Study of Release Kinetics of Ibrufen, Entrapped in Nanoporous Silica Gel As Potential Drug Carrier PDF

STUDY OF RELEASE KINETICS OF IBRUFEN, ENTRAPPED
IN NANOPOROUS SILICA GEL AS POTENTIAL DRUG

CARRIER
A thesis submitted towards partial fulfillment of the requirements for the degree of
Master of Technology in Nano Science & Technology
Submitted by
MD MODASSIR ANWER
EXAMINATION ROLL NO: M4NST1709
Under the guidance of

DR. MAHUA GHOSH CHAUDHURI
School of Materials Science & Nanotechnology
Jadavpur University
Course affiliated to
Faculty of Engineering and Technology
Jadavpur University
Kolkata-700032
India
2017
M.Tech in Nano Science & Technology
Course affiliated to
Faculty of Engineering and Technology
Jadavpur University
Kolkata, India
_________________________________________________________________
CERTIFICATE OF RECOMMENDATION
This is to certify that the thesis entitled “STUDY OF RELEASE KINETICS

OF IBRUFEN, ENTRAPPED IN NANOPOROUS SILICA GEL AS
POTENTIAL DRUG CARRIER” is a bonafide work carried out by Md
Modassir Anwer under my supervision and guidance for partial fulfillment of
the requirement of Master ofTechnology in Nano Science & Technology
under School of MaterialsScience & Nanotechnology, during the academic
session 2015-2017.
------------------------------------------------ ------------------------------------------------------------
DR. MAHUA GHOSH CHAUDHURI DR. KALYAN KUMAR CHATTOPADHYAY

Assistant Professor, Director,
School of Materials Science School of Materials Science &
& Nanotechnology, Nanotechnology,
Jadavpur University, Jadavpur University,
Kolkata-700032 Kolkata- 700032
-------------------------------------------------
DEAN -FISLM
Jadavpur University,
Kolkata-700 032
CERTIFICATE OF APPROVAL
This foregoing thesis is hereby approved as a credible study of an

engineering subject carried out and presented in a manner
satisfactorily to warranty its acceptance as a pre-requisite to the
degree for which it has been submitted. It is understood that by
this approval the undersigned do not endorse or approve any
statement made or opinion expressed or conclusion drawn therein
but approve the thesis only for purpose for which it has been
submitted.
Committee of final examination for evaluation of Thesis
1. ---------------------------------------
2. ---------------------------------------
3. ---------------------------------------
4. ---------------------------------------
DECLARATION OF ORIGINALITY AND COMPLIANCE OF
ACADEMIC ETHICS
I the undersigned hereby declare that this thesis contains literature survey
and original research work being submitted, as part of my M. Tech Degree
in Nano Science & Technology during academic session 2015-2017. All
information in this document has been obtained and presented in accordance
with academic rules and ethical conduct. I also declare that, as required by
this rules and conduct, I have fully cited and referred all material and results
that are not original to this work.
NAME: MD MODASSIR ANWER

EXAMINATION ROLL NUMBER: M4NST1709
THESIS TITLE: STUDY OF RELEASE KINETICS OF IBRUFEN, ENTRAPPED IN
NANOPOROUS SILICA GEL AS POTENTIAL DRUG CARRIER
DATE: SIGNATURE
DEDICATED TO
ALL WHO
INSPIRED ME& MY FAMILY FOR THE WORK
Acknowledgement
The satisfaction and euphoria that accompany the successful completion of

any task would be incomplete without the mentioning of the people whose
constant guidance and encouragement made it possible. I express my earnest
gratitude to my guide Dr. Mahua Ghosh Chaudhuri, Assistant Professor,
School of Materials Science & Nanotechnology, Jadavpur University,
Kolkata for his constant support, encouragement and guidance. I am grateful
for his cooperation and his valuable suggestions.
I would like to thank Pritha Pal, PhD Research Scholar, School of Materials
Science & Nanotechnology, Jadavpur University for her help and support.
I also want to thank the XRD, FTIR, FESEM, TEM, UV-VIS, PL and
Electrochemical analysis facilities in School of Material science and
Nanotechnology, Dept. of Physics, School of Laser Science, Dept. of
Chemical Engineering of Jadavpur University and lastly CGCRI, Jadavpur,
Kolkata for their cooperation and helping me out with the successful
completions of my work.
I express my gratitude to all other members of the Dept. of Nanotechnology
and my friends who are involved either directly or indirectly for the
successful completion of this project.
Last but not the least; I would like to thank my family for supporting me
throughout my life.
CONTENTS
1. CHAPTER-1
INTRODUCTION 1-19
1.1What is nanotechnology 2
1.2 Nanomaterials 3
1.3 Synthesis procedures of nanomaterials 4
1.3.1 Top-down approach 4
1.3.2 Bottom-up approach 4
1.4Sol-gel 5
1.4.1 Sols, Gels, and Aerogels are Colloids 6
1.4.2 Production of Sols 7
1.4.3 The Sol-Gel Transition 7
1.4.4 Factors that Affect Sol-Gel Chemistry 8
1.5Applications of nanotechnology 9
1.5.1 Nano-biotechnology
1.6 Drug and drug carrier 11
1.7 Drug administration routes 12
1.8 Ibuprofen 16
1.8.1 Mechanism of action 17
1.8.2 Stereochemistry 18
REFERENCES
2. CHAPTER-2
LITERATURE REVIEW 23-38
2.1 Preparation of Silica gel by sol gel process 24

2.2 Silica gel as drug carrier 25
2.3 Drug release 26
2.4 characteristics that makes drugs suitable for sustained release 30
2.5 Advantages of sustained release drug delivery over conventional 31
Like burst release forms
2.6 Release kinetics 31
2.6.1 Zero-order model 32
2.6.2 First order 33
2.6.3 Higuchi model 34
2.6.4 Korsmeyer-Peppas model 35
2.7 Different type of analgesic 36
2.8 General drug delivery 37
REFERENCES
3. CHAPTER-3 41-42
OBJECTIVES
4. CHAPTER-4 43-47
METHODOLOGY
4.3 Characterization of Silica gel using XRD, FTIR, FESEM 46

4.4 Preparation of Simulated body Fluid formation 46
4.5 Study of Release Mechanism 47
5. CHAPTER-5
CHARACTERIZATION TECHNIQUES 48-63
5.1 X-Ray Powder Diffraction analysis 49

5.2 UV-Vis Spectrophotometer analysis 55
5.3 FTIR (Fourier Transform Infrared Spectroscopy) analysis 58
5.4 Field Emission Scanning Electron Microscope(FESEM) 61
6. CHAPTER-6
RESULTS AND DISCUSSION 65-100
6.1 Characterization of Silica gel using XRD 66

6.2 FESEM analysis 68
6.3 FTIR analysis 70
6.4 UV-Vis spectroscopy analysis 78
6.5 Kinetic study of drug release 79
7. CHAPTER-7
CONCLUSION 101-102
LIST OF FIGURES
Figure Page No
1.1. Schematic diagram of nanomaterial synthesis --------------------------------------------- 5

1.2. Combination of nano-biotechnologies for the development of nano-medicine ------- 10
1.3. Structural formula of Ibrufen (C13H18O2 ) ------------------------------------------------- 16
1.4. Structural formula of (R)-Ibrufen and (S)-Ibrufen ---------------------------------------- 19
2.1. Graph shows the difference between Zero-order and burst release dosage forms----- 27
2.2. Graph shows the difference between the conventional and sustained ------------------ 28
Release dosage forms
5.1. Schematic diagram of X-RAY --------------------------------------------------------------- 50
5.2. Inter planar spacing diagram of particles --------------------------------------------------- 52
5.3. Schematic diagram of an X-RAY diffraction peak to measure the FWHM ----------- 53
5.4. Photograph of Rigaku Ultima III X-ray Diffractometer ---------------------------------- 54
5.5. Basic diagram of UV-Vis spectrophotometer ---------------------------------------------- 57
5.6. Schematic diagram of FTIR ------------------------------------------------------------------ 59
5.7. Photograph of Shimadzu IRPrestige-21 FTIR spectrometer ----------------------------- 60
5.8. Components of FESEM ----------------------------------------------------------------------- 62
5.9. Field emission scanning electron microscopy (FESEM) coupled with ----------------- 63
EDAX (Hitachi S 4800).
6.1(a). XRD pattern of bare silica gel in TEOS: ETOH: DI WATER (1:2:1) ratio -------- 66
6.1(b). XRD pattern of bare silica gel in TEOS: ETOH: DI WATER (1:2:2) ratio -------- 67
6.12(a) & (b). FESEM of bare silica gel of TEOS: ETOH: DI WATER in (1:2:1) ratio-- 68
6.13(a) & (b). FESEM of bare silica gel of TEOS: ETOH: DI WATER in (1:2:2) ratio-- 69
6.2(a). FTIR of Solid Ibrufen entrapped with silica gel matrix of --------------------------- 70
TEOS: ETOH: DI WATER (1:2:1) ratio
6.2(b). FTIR of Solid Ibrufen entrapped with silica gel matrix of --------------------------- 72
6.2(c). FTIR of Liquid Ibrufen entrapped with silica gel matrix of -------------------------- 74
TEOS: ETOH: DI WATER (1:2:1) ratio.
6.2(d). FTIR of Liquid Ibrufen entrapped with silica gel matrix of -------------------------- 76
TEOS: ETOH: DI WATER (1:2:2) ratio.
6.3(a). Standard Curve of Liquid Ibrufen -------------------------------------------------------- 78
6.3(b). Standard Curve of Solid Ibrufen --------------------------------------------------------- 79
6.4(a). Zero-order release model (b) First-order release model (c) Higuchi release ----- 80
model (d) Korsmeyer-Peppas release model:
model (d) Korsmeyer-Peppas release model
6.6(a). Zero-order release model (b) First-order release model (c) Higuchi release ------ 85
model (d) Korsmeyer-Peppas release model.
6.10(a). Zero-order release model (b) First-order release model (c) Higuchi release ---- 95
6.11(a). Zero-order release model (b) First-order release model (c) Higuchi release ---- 98
LIST OF TABLES
Table Page No
1. Advantages and Disadvantages of Drug Administration Routes ----------------------- 13

2. The value of nthat characterizes the release mechanism ---------------------------------- 35
3. Composition of SBF -------------------------------------------------------------------------- 47
4. FTIR of Solid Ibrufen entrapped with silica gel matrix of ------------------------------ 71
5. FTIR of Solid Ibrufen entrapped with silica gel matrix of ------------------------------ 73
6. FTIR of Liquid Ibrufen entrapped with silica gel matrix of ---------------------------- 75
7. FTIR of Liquid Ibrufen entrapped with silica gel matrix of ---------------------------- 77
ABSTRACT
Silica gel is prepared at room temperature from Tetraethyl Ortho-Silicate (TEOS), Ethyl
alcohol and DI water precursor. Ibrufen in solid and liquid form is entrapped into porous sol-
gel derived silica gel. Fourier transform infrared analysis (FTIR) revealed the proper
entrapment of Ibrufen in the Nano-pores of the silica gel. The release kinetics of Ibrufen in
Simulated Body Fluid (SBF) of pH 7.0 is determined using UV-Vis spectroscopy. SBF
contain the released Ibrufen from Silica gel collected after different time interval. Kinetics
study of release of Ibrufen hum silica gel SBF is studied and it is found to follow zero order
kinetics model for both burst and sustain release.

CHAPTER 1
INTRODUCTION
1
1.1 What is Nanotechnology?
Nano stands very small which ranges near 1 to 100 nanometers (nm)or10-9 m and having large
applications through all the discipline of knowledge, innovative ideas, thoughts leading to
commercial, industrial and technological growth. Reducing the size of a bulk material to
nanometer size, its properties get drastically changes [1]. Nano-scale is so special as materials
show different properties like some having different magnetic properties, better heat and
conducting electricity, some are stronger, some reflect light better and changes colors as size
is changed. In other words nano-sized structure needs to be magnified over large region 10
million times before we can easily study its detail with the naked eye [2].
To define the nanotechnology lot of consideration is there behind our thoughts,
views and ideas. It is defined as being concerned with materials and systems whose structures
and components exhibit novel and significantly improved physical, chemical and biological
properties, phenomena and processes due to their nano scale size [3].
Studies in nanotechnology have induced great scientific advancement in the field
of research and technology. Nanotechnology is the study of small object which can be used
across all fields such as chemistry, biology, physics, material science and engineering.
Nanotechnology is emerging as a manufacturing new material at the nanoscale level (Albrecht
et al., 2006). The prefix „nano‟ indicates one billionth or 10−9 units. The advantage of using
nanomaterials with diameter of <100nm in number of applications is widely being research in
many field such as physics, chemistry, optical components, electronics, mechanical
engineering. Over the last few years‟ applications of nanometer materials have received
tremendous significance. Many fields of nanotechnology are based on physical and chemical
interaction involving nanostructured material of particular shape and size. Various methods of
synthesis and interaction mechanisms have widely been studied which has led to the
development of low cost, low power and portable technology in the field of agriculture, fuel
cell, biomedical, agriculture, chemistry, physics, manufacturing and many more in the future.
The properties of nanodimensional materials change significantly because of increased

surface area and quantum effect.
2
1.1.1 Increased surface area:
As a particle decreases in size, a greater proportion of atoms are found at the surface
compared to those inside. For example, a particle of size 30 nm has 5% of its atoms on its
surface, at 10 nm 20% of its atoms, and at 3 nm 50% of its atoms. As the surface area
increases the number of broken bonds increase accordingly making the Particle more reactive.
1.1.2 Quantum effect:
In tandem with surface-area effects, quantum effects can begin to dominate the properties of
matter as size is reduced to the nanoscale. These can affect the optical, electrical and magnetic
behavior of materials, particularly as the structure or particle size approaches the smaller end
of the nanoscale. Materials that exploit these effects include quantum dots, and quantum well
lasers for optoelectronics.
By controlling the particle size, assembly of atoms, structures, composition and growth
mechanism, it is possible to improve existing devices, structures and materials. Even though
nano structures or nanomaterials are not new, but the new thing in nanotechnology is we can
at least partially understand and control these structures and properties to fabricate new
functional materials and devices. We are in the era of engineered nano materials and devices
as molecular machine has become a reality as Feynman predicted.
1.2 Nanomaterials:
The nanomaterials field includes subfields which develop or study materials having unique
properties arising from their nanoscale dimensions [1].
 Interface and colloid science has given rise to many materials which may be useful in
nanotechnology, such as carbon nanotubes and other fullerenes, and various
3
nanoparticles and nanorods. Nanomaterials with fast ion transport are related also to
nanoionics and nanoelectronics.
 Nanoscale materials can also be used for bulk applications; most present commercial
applications of nanotechnology are of this category.
 Progress has been made in using these materials for medical applications; see
nanomedicine.
 Nanoscale materials are sometimes used in solar cells which combats the cost of
traditional Silicon solar cells.
 Development of applications incorporating semiconductor nanoparticles to be used in
the next generation of products, such as display technology, lighting, solar cells and
biological imaging; see quantum dots.
1.3 Synthesis procedures of nanomaterials:
The synthesis procedure of nanomaterials can be broadly categorized in two techniques:
1.3.1 Top-down approach: Top down approach refers to slicing or successive cutting of
a bulk material to get nano sized particle. There are advantages and disadvantages in both
approaches. The biggest problem with top down approach is the imperfection of surface
structure and significant crystallographic damage to the processed patterns. These
imperfections which in turn leads to extra challenges in the device design and fabrication. Top
down approach most likely introduces internal stress, in addition to surface defects and
contaminations. But this approach leads to the bulk production of nano material. Regardless
of the defects produced by top down approach, they will continue to play an important role in
the synthesis of nano structures.
1.3.2 Bottom-up approach: Bottom up approach refers to the build-up of a material

from the bottom: atom by atom, molecule by molecule or cluster by cluster. When structures
4
fall into a nanometer scale, there is a little chance for top down approach. All the tools we
have possessed are too big to deal with such tiny subjects. Bottom up approach also promises
a better chance to obtain nano structures with less defects, more homogeneous chemical
composition.
Synthesis Procedure
of nanomaterials
Top Down Approach
• Mechanical Grinding
• Erosion
• Vapour Treatment
• Micropatterning
• Lithography etc.
Bottom Up Approach
• Sol-gel Process
• Aerosol-Based Processes
• Chemical Vapour Deposition
(CVD)
• Atomic or Molecular
Condensation
• Self-Assembly etc.
Figure 1.1: schematic diagram of nanomaterial synthesis.
1.4 SOL-GEL:
The term sol-gel (say “sahl-jell”) refers to a process in which solid nanoparticles dispersed in
a liquid (a sol) agglomerate together to form a continuous three-dimensional network
extending throughout the liquid (a gel). The term sol-gel is sometimes used as a noun to refer
5
to gels made through the sol-gel process, but this is somewhat of an abuse of the term, since
pretty much all gels are made through the sol-gel process [4].
1.4.1 Sols, Gels, and Aerogels are Colloids:

A colloid is a mixture in which at least two different phases are intimately mixed at the
nanolevel. The term “phase” generally refers to a solid, liquid, or gas form of some substance.
A colloid typically has a continuous phase in which something else with a different phase is
dispersed (the “dispersed phase”). Different phases can still be the same phase of matter, for
example, two different phases could both be liquids, just not miscible liquids.
Colloids are different from homogeneous solutions, in which a substance is dissolved or
mixed with another substance and does not separate out, in that the components of colloids
are nanoparticles or macromolecules (giant molecules), typically with a length or diameter
ranging from a few nm to several hundred nm in diameter.
Sol: A sol is a liquid. The continuous phase in a sol is a liquid and the dispersed phase is a
solid. The difference between a sol and a non-colloidal liquid is that solid nanoparticles are
dispersed throughout the liquid in a sol. If you put a sol in a centrifuge, you can force the
nanoparticles dispersed in the liquid to precipitate out. This will not happen for a non-
colloidal liquid solution, for example, salt dissolved in water.
An example of a sol is black inkjet ink (carbon black dispersed in water).
Gels: A gel is a wet solid like material in which a solid network of interconnected
nanostructures spans the volume of a liquid medium. The continuous phase is a solid network
and the dispersed phase is a liquid. Gels tend to be mostly liquid in composition and typically
exhibit the density of a liquid as result but have cohesiveness like a solid.
An example of a gel is Jell-OTM gelatin.
Aerogels: An aerogel is solid with air pockets dispersed throughout. Aerogels are
essentially the solid framework of a gel isolated from the gel‟s liquid medium. Some aerogels,
6
such as carbon aerogels and iron aerogels, are derived from other types of aerogels, but the
aerogels they‟re derived from came from a gel directly.
1.4.2 Production of Sols:
Sols of all sorts of compositions can be made several different ways. Nanoparticles of any
solid dispersed in any liquid in such a way that the solid phase does not spontaneously
precipitate or settle out is considered a sol.
Generally there are two ways sols are made:
Nanoparticles are grown directly in a liquid: This happens when you make Jell-O, or a
silica gel. Basically you mix ingredients that contain molecules that can interconnect together
to form bigger molecules and eventually nanoparticles. These nanoparticles then hook up
together to form a gel network.
Nanoparticles are synthesized and then dispersed in a liquid: This is how more advanced
gels are made. Nanoparticles such as quantum dots or carbon nanotubes are made through
some process and then dissolved in a liquid directly or dispersed using the help of a surfactant
(a detergent, like shampoo or dish soap). This is how metal chalcogenide aerogels and carbon
nanotube aerogels start out. In the case of quantum dots, these nanoparticles are usually
synthesized in a liquid, centrifuged out, and then redissolved in the desired liquid medium for
whatever you‟re using them for. Carbon nanotubes, on the other hand, are grown at high
temperatures outside of a liquid medium.
1.4.3 The Sol-Gel Transition:

A sol can become a gel when the solid nanoparticles dispersed in it can join together to form a
network of particles that spans the liquid. This requires that the solid nanoparticles in the
liquid, which are constantly bouncing around in random directions because of temperature
(that is, they are undergoing Brownian motion), bump into each other and stick together when
they do. For some nanoparticles this is easy, almost automatic, since they contain reactive
surface groups that condense together to form bonds. For other nanoparticles, however, this
can be tricky and requires the addition of an additive to “glue” the particles together or
removal something from the particle surfaces so that they stick together when collide, either
by bonding together or by electrostatic forces (static electricity). As a sol becomes a gel, its
7
viscosity approaches infinity and finally becomes immobile (that it is, it stops being able to
flow and fill its container, although it might still wobble back and forth). This transition from
sol to gel is called gelation. The point in time when the particle network extends across the
entire volume of the liquid causing it to immobilize is called the gel point. The time required
for a gel to form after mixing stuff together to make the gel is called the gel time.
1.4.4 Factors that Affect Sol-Gel Chemistry:
pH: Any colloidal chemistry that involves water is sensitive to pH. In the case of silica gel
formation, this has to do with the hydrolysis step of the silica precursor that results in silanol
groups, which are what connect together to produce silica nanoparticles and eventually the gel
network.
Temperature: The chemical kinetics of the different reactions involved in the formation of
nanoparticles and the assembly of nanoparticles into a gel network are accelerated by
temperature, meaning the gel time is affected by temperature. If the temperature is too low,
gelation may take weeks or months. If the temperature is too high, the reactions that join
nanoparticles together into the gel network occurs so quickly that clumps form instead and
solid precipitates out of the liquid.
Time: Depending on the type of gel being made, different steps in the gel formation process
work differently over different time scales. In general, slower is better for sol-gel. If a gel is
allowed to form slowly, it usually has a much more uniform structure. This often means a
stronger gel and, in the case of potentially transparent gels like silica, results in a clearer gel
that Rayleigh scatters less (appears less blue). Speeding reactions up too many causes
precipitates to form instead of gel network, and can make a gel cloudy and weak or simply not
form.
8
1.5 Applications of nanotechnology:
Nanotechnology and its development get the new dimensions, as the development of
nanotechnology as the latest field in science and engineering which will bring a wave of
radical innovation and because of its potentially broad impact, spark new industrial revolution
in various application areas. Areas of applications include impact - drug delivery to treat
tumor, cancer (without using radiotherapy & chemotherapy), solar energy, batteries, display
technologies, optoelectronic devices, semiconductor nanostructure devices in nano-
electronics, biosensors, CNT's etc., nano-composites such as Al2O3 oxides, catalysis, and
luminous paints. This is an applied science of systems and devices as dimensions measured in
nanometers with scales towards molecular or atomic levels. Different sciences come together
to study the micro-design of new products and devices with large applications.
Nanotechnology is already having its impact on products as novel foods, medical devices,
printing equipment, chemical coatings, personal health testing kits or healthcare devices,
automotive parts to telecommunication hardware sensors for security systems, water
purification units for manned space craft, and high-resolution cinema screens, and displays for
computer games. Nanotechnology is expected to have big demand on nearly every industry
[4].
Three major sectors are listed as below:
 Nano-electronics.
 Nano-biotechnology.
 Nano-materials.
Out of these major sectors Nano-biotechnology has rapid developing field in nanotechnology.
Nano-biotechnology is a highly interdisciplinary field. Let us discuss in brief.
1.5.1 Nano-biotechnology:
Nano-biotechnology is termed describing the junction of the two existing but isolated worlds
of engineering and molecular biology. It is a combination of three words: “nano” tiny, “bio” is
9
living things, and “technology” is about tools. It refers to the ability to create and manipulate
biological and biochemical materials, devices, and systems at atomic and molecular levels.
Thus, it is an integration of physical sciences, molecular engineering, biology, chemistry, and
biotechnology. It holds considerable promise of advances in pharmaceuticals and health care.
Nano-materials are at the leading edge of the rapid developing field of nanotechnology. Their
unique size-dependent properties make these materials superior, crucial in many areas of
human activity, and above all a tiny tool to learn about living things [5]. In health care and
medicine biological nano-sensors are being developed in the next 10 years and will be used
for fast and accurate diagnostics. Further ahead, nanotechnology may be used to build
artificial muscle and 'lab on a chip' technology will develop more efficient drug discovery
processes. There are many other future applications of nanotechnology and more possibilities
will come to light as it is developed further. Nanotechnology offers major opportunities for
the UK economy and that it is allowed to thrive, building upon the countries excellence in its
science and technology base. Critics of nanotechnology insist that a strict regulatory system
should be introduced to ensure risks are minimized and it is the government's responsibility to
ensure that procedures are put in place to ensure that this happens. In recent years, great
progress was achieved in making drugs own the characteristics of targeted and controlled
release via nanotechnologies.
Figure 1.2: Combination of nano-biotechnologies for the development of nano-medicine.
10
Drug is wrapped in or adsorbed on surface of nanoparticles, when the specific targeting
molecules combining with the receptor of cell surface, nano-drug is taken into cells, to
achieve the safe and effective targeted drug delivery and gene therapy. Because Nano-drug
carriers have high targeting, favorable sustained, controlled release capability and superior
cell penetration ability, it can improve efficacy of drugs and reduce side effects. Another
important thing that the nano-structure by changing its different composition and ratio. It
naturally formed biomolecule and material particle, in effect redefining much of chemistry
and molecular biology as 'nano biotechnology [6].
1.6 Drug and drug carrier:
Nano-biomaterials are a new type of drug carriers with very promising application. In recent
years, great progress was achieved in making drugs own the characteristics of targeted and
controlled release via nanotechnologies. A drug carrier is used in the drug delivery process
which serves to improve the selectivity, effectiveness, and safety of drug administration. Drug
carriers are primarily used to control the release of a drug into systemic circulation. This can
be consist either by slow release of the drug over a long period of time (typically diffusion) or
by triggered release at the drug's target by some stimulus, like changes in pH, application of
heat, and activation by light. Drug carriers generally lipid-based, polymeric and inorganic
types are used to improve the pharmacokinetic properties, specifically the bioavailability, of
many drugs with poor water solubility and/or membrane permeability [7].
When drug is wrapped in or adsorbed on surface of nanoparticles, when the specific targeting
molecules combining with the receptor of cell surface, nano-drug is taken into cells, to
achieve the safe and effective targeted drug delivery and gene therapy. Because Nano-drug
carriers have high targeting, favorable sustained, controlled release capability and superior
cell penetration ability, it can improve efficacy of drugs and reduce side effect.
In recent years, delivery strategies integrated with emerging micro- or nanotechnologies have
attracted more and more attention. The general idea is to encapsulate insulin into specific
carriers like micro or nano scale for effective delivery. Drug carrier has a tendency to control
the release and high surface areas thereby having following advantages are [8]:
11
1. Drug carriers can enter into capillaries and flow in blood circulation freely so enhance
bioavailability of drug.
2. Specific surface area of drug carriers is very high; solubility of poor water-soluble drugs
in Nano-carrier is enhanced.
3. Nano-carrier extends biological half- life of drug, improve efficacy of short half -life
drugs and reduce side effects of medication.
4. Nano-carriers can be made to target position in system thereby minimize the dose of
drug and reduced side effects.
A pharmaceuticals drug is a chemical substance which is used for the diagnosis, treatment or
prevention of diseases. Drugs are administered as a primary form of therapy or in adjunction
to another mode of therapy. All the effective drugs which are used by physicians have certain
adverse effects along with therapeutic effects. The judgment to administer the drug is based
on the risk/benefit ratio. The process of bringing a new drug to the consumers is divided into
several stages: target/disease identification, hit identification/discovery, hit optimization, lead
selection and further optimization, candidate identification, clinical methods and proper
medication [9].
1.7 Drug administration routes:
Drug delivery is the method or process of administering a pharmaceutical compound to

achieve a therapeutic effect in humans or animals. The different routes of administration of
drug can be broadly classified into Enteral and Parenteral. Enteral route uses the
gastrointestinal tract, including the oral, sublingual/buccal and rectal. Parenteral route does
not use the alimentary canal and refers to injections. Parenteral may also use topical,
inhalation and transdermal as methods of drug administration. Each of these routes has their
own advantages and disadvantages [10].
Table 1: Advantages and Disadvantages of Drug Administration Routes in general discussed:
12
Routes Advantages Disadvantages
Oral Convenient, portable, easy to High doses and poor solubility
Administer drugs have low bioavailability
Pain free administration Slow and unpredictable

absorption due to degradation
No need for sterilization of stomach acids and enzymes
Variety of dosages forms like
fast
release, slow release, enteric
coating, etc. are available
Buccal Liver is bypassed and hence Holding doses in the mouth is
the first Inconvenient. Slowing leads
pass effect is avoided, to the
leading to dosage being treated as oral
Improved bioavailability
Suitable for drugs with small
Rapid absorption doses
Drug stability is good due to Taste needs to be masked

neutral
pH in the mouth
Rectal First pass effect is reduced Erratic absorption
Useful if oral administration Leads to discomfort

is not
possible
Subcutaneous/ Rapid response Finding suitable veins may be
a problem
13
Intramuscular/ Best bioavailability
Toxicity may be high
Intravenous Larger doses can be given
and time of administration Requires trained personnel
can be controlled in case of
IV Expensive
Veins are insensitive to Patient compliance is poor

presence of
irritants Irritants can cause local tissue
damage and pain.
Inhalation Rapid absorption due to Bioavailability depends on
bypassing of the liver and inhalation technique, size of
large surface area of drug particles
respiratory endothelium
Some portion of the drug may
be
swallowed
Topical/ Local effects can be achieved Very slow and poor
Transdermal by eye absorption
drops, ear drops, ointments
May cause irritations
Easy to administer
Non invasive
Patient compliance is high
The body contains several barriers and mechanisms. It protects its interior from external
invasions such as toxins and pathogens. The skin forms the largest barrier. For orally
14
administered drugs to be absorbed, it has to cross the gastrointestinal epithelium. The blood-
brain barrier also forms a tight barrier to the traversal of molecules from the blood to the
brain. The obstruction to drug delivery may be categorized as physiological, biochemical and
chemical. These barriers have to be considered in while designing drugs as well as drug
delivery systems [11].
Drug formulation and delivery administers a drug at a therapeutic concentration to a particular

site of action for a specified period of time. The final formulated product for drug delivery
depends upon several factors. First, the drug must be administered using a narrow set of
parameters that are defined by the therapeutic action of the drug including the site of action
(either targeted to a specific region of the body or systemic), the concentration of the drug at
the time of administration, the amount of time the drug must remain at a therapeutic
concentration, and the initial release rate of the drug for oral/controlled release systems.
Degradation of the drug releases very slowly in site of action. The drug must remain
physically and chemically stable in the formulation for at least 2 years. The choice of delivery
method must reflect the preferred administration route for the drug, such as oral, parenteral, or
transdermal [12].
Drug Delivery Systems enable the introduction of a therapeutic agent into the body by means
of a formulation or device and improves the efficacy and safety of the agent by controlling
rate, time and place of release of the drug. Drug delivery systems are classified as the
following [13]:
1. Delayed Release.
2. Sustained Release.
3. Site-specific Targeting.
4. Receptor Targeting.
A controlled drug delivery system is usually designed to deliver the drug at particular rate.
Safe and effective blood levels are maintained for a period as long as the system continues to
deliver the drug. Controlled drug delivery usually results in constant blood levels of the active
15
ingredient as compared to the uncontrolled fluctuations observed when multiple doses of
quick releasing dosage forms are administered to a patient [14].
1.8 Ibuprofen:
Inflammatory drug (NSAID) class that is used for treating pain, fever, and inflammation. This
includes painful menstrual periods, migraines, and rheumatoid arthritis [15]. About 60% of
people improve with any given NSAID, and it is recommended that if one does not work then
another should be tried. It may also be used to close a patent ductus arteriosus in a premature
baby. It can be used by mouth or intravenously. It typically begins working within an hour.
Common side effects include heartburn and a rash. Compared to other NSAIDs it may have
fewer side effects such as gastrointestinal bleeding [16].
Figure 1.3: structural formula of Ibrufen ( C13H18O2 ).
It increases the risk of heart failure, kidney failure, and liver failure. At low doses, it does not
appear to increase the risk of myocardial infarction; However, at higher doses it may.
16
Ibuprofen can also result in worsened asthma. While it is unclear if it is safe in early
pregnancy, it appears to be harmful in later pregnancy and therefore is not recommended [17].
Like other NSAIDs, it works by inhibiting the production of prostaglandins by decreasing the
activity of the enzyme cyclooxygenase. Ibuprofen might be a weaker anti-inflammatory than
other NSAIDs.
1.8.1 Medical uses:

Ibuprofen is used primarily to treat fever (including postimmunisation fever), mild to
moderate pain (including pain relief after surgery), painful menstruation, osteoarthritis, dental
pain, headaches, and pain from kidney stones. About 60% of people respond to any NSAID;
those who do not respond well to a particular one may respond to another [18]. It is used for
inflammatory diseases such as juvenile idiopathic arthritis and rheumatoid arthritis [19-20]. It
is also used for pericarditis and patent ductus arteriosus [21].
1.8.2 Mechanism of action:

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen work by inhibiting the
cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandin H2 (PGH2).
PGH2, in turn, is converted by other enzymes to several other prostaglandins (which are
mediators of pain, inflammation, and fever) and to thromboxane A2 (which stimulates platelet
aggregation, leading to the formation of blood clots). Like aspirin and indomethacin,
ibuprofen is a nonselective COX inhibitor, in that it inhibits two isoforms of cyclooxygenase,
COX-1 and COX-2. The analgesic, antipyretic, and anti-inflammatory activity of NSAIDs
appears to operate mainly through inhibition of COX2, which decreases the synthesis of
prostaglandins involved in mediating inflammation, pain, fever, and swelling. Antipyretic
effects may be due to action on the hypothalamus, resulting in an increased peripheral blood
flow, vasodilation, and subsequent heat dissipation. Inhibition of COX1 instead would be
responsible for unwanted effects on the gastrointestinal tract[22]. However, the role of the
individual COX isoforms in the analgesic, anti-inflammatory, and gastric damage effects of
NSAIDs is uncertain and different compounds cause different degrees of analgesia and gastric
17
damage.[40] Ibuprofen is administered as a racemic mixture. The R-enantiomer undergoes
extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is believed to be the
more pharmacologically active enantiomer [23]. The R-enantiomer is converted through a
series of three main enzymes. These enzymes include acyl-CoA-synthetase, which converts
the R-enantiomer to (-) - R-ibuprofen I-CoA; 2-arylpropionyl-CoA epimerase, which
converts (-) - R-ibuprofen I-CoA to (+) –S-Ibuprofen I-CoA; and hydrolase, which converts
(+)S-ibuprofen I-CoA to the S-enantiomer. In addition to the conversion of ibuprofen to the S-
enantiomer, the body can metabolize ibuprofen to several other compounds, including
numerous hydroxyl, carboxyl and glucuronyl metabolites. Virtually all of these have no
pharmacological effects [24].
1.8.3 Stereochemistry:
Ibuprofen is practically insoluble in water, but very soluble in most organic solvents like
ethanol (66.18 g/100mL at 40°C for 90% C2H5OH), methanol, acetone and dichloromethane
[25]. The original synthesis of ibuprofen by the Boots Group started with the compound
2methylpropylbenzene. The synthesis took six steps. A modern, greener technique for the
synthesis involves only three steps [26].
It is an optically active compound with both S and R-isomers, of which the S (dextrorotatory)
isomer is the more biologically active; this isomer has also been isolated and used medically
(see dexibuprofen for details). Ibuprofen is produced industrially as a racemate. The
compound, like other 2arylpropionate derivatives (including ketoprofen, flurbiprofen,
naproxen, etc.), does contain a chiral center in the αposition of the propionate moiety. So two
enantiomers of ibuprofen occur, with the potential for different biological effects and
metabolism for each enantiomer. Indeed, the (S)-(+)-ibuprofen (dexibuprofen) was found to
be the active form both in vitro and in vivo.
An isomerase (alpha-methylacyl-CoA racemase) converts (R)-ibuprofen to the active (S)-
enantiomer [27-28].
18
Figure 1.4: structural formula of (R)-Ibrufen and (S)-Ibrufen
19
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Ceramics in Medical Devices: Applications and Prospects", CR (2004). 38–43.
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and three-dimensional nanostructured materials for advanced electrochemical energy
devices. Prog Mater Sci (2012 )724-803.
3. Spencer MJS, Gas sensing applications of 1D-nanostructured zinc oxide: insights from
density functional theory calculations. Prog Mater Sci 2012, 57:437-86.
4. Aerogel.org. The sol-gel process.
5. https://web.stanford.edu/dept/EHS/prod/researchlab/IH/nano/what_are_nanomaterials.ht
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6. J. Kawadkar, M k. Chauhan and M Maharana, Nano-biotechnology: application of
nanotechnology in diagnosis, drug discovery and drug development, Asian Journal of
Pharmaceutical and Clinical Research, vol. 4, issue 1, 2011.
7. Jain KK. Nano-biotechnology: applications, markets, and companies. Basel: Jain
Pharma Biotech Publications
8. Yong Liu, Tian-Shui Niu, Long Zhang, Jian-She Yang. "Review on nano-drugs."
Natural Science Vol.2( 1) 2010: 41-48.
9. Binghe Wang, Teruna Siahaan, Richard Soltero. Drug Delivery: Principles and
Applications. John Wiley and Sons, Inc, 2005.
10. S. Chakraborty, J. S. Mannaa, S. Das, M. K. Mitra, R.Dey, Sustained release of silica
gel entrapped herbal values and their antimicrobial activity, Asian Journal of
Pharmaceutical and Clinical Research, vol. 4, issue 2, 2011.
11. Bourne, David W.A. "PHAR 7633 Chapter 7 Routes of Drug Administration." Boomer
Home Page. Jan 14, 2014. http://www.boomer.org/.
12. Gaurav Tiwari, Ruch Tiwari, Birendra Sriwastawa, L Bhati, S Pandey, P Pandey,
Saurabh K Banerjee." Drug Delivery Systems: An updated review." International
Journal of Pharmaceutical Investigation Vols. 2(1) 2012: 2–11. [12] Bajaj Amruta,
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Katedeshmukh Ramesh. " Oral Controlled Drug Delivery System." In Drug Delivery
Systems: A Review, by A.V Gothaskar. 2004.
13. Bajaj Amruta, Katedeshmukh Ramesh. " Oral Controlled Drug Delivery System." In
Drug Delivery Systems: A Review, by A.V Gothaskar. 2004.
14. Chia-Hung Lee, Leu-Wei Lo, Chung Yuan Mou, Chung-Shi Yang. "Synthesis and
Characterization of Positive-Charge Functionalized Mesoporous Silica Nanoparticles for Oral
Drug Delivery of an Anti-Inflammatory Drug." Adv. Funct. Mater Vol 18: 3283–3292.
15. DaeYong Lee,a Kibaek Choe,b YongJun Jeong,a Jisang Yoo,a Sung Mun Lee,c,Ji-Ho
Park,d Pilhan Kimb and Yeu-Chun Kim, RSC Adv., 2015, 5, 14482
16. "Ibuprofen" (http://www.drugs.com/monograph/ibuprofen.html). The American Society
of HealthSystem Pharmacists. Retrieved 20161012.
17. Bnf : march 2014september 2014. (2014 ed.). London: British Medical Assn. 2014. pp.
686–688. ISBN 0857110861.
18. "Ibuprofen Pregnancy and Breastfeeding Warnings"
(http://www.drugs.com/pregnancy/ibuprofen.html). Drugs.com. Retrieved 22 May 2016.
19. "10.1.1 Nonsteroidal anti-inflammatory drugs"
(https://www.evidence.nhs.uk/formulary/bnf/current/10musculoskeletalandjointdiseases/
101drugsusedinrheumaticdiseasesandgout/1011nonsteroidalantiinflammatorydrugs).
British National Formulary. Retrieved 13 April 2016.
20. Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.).
London, UK: Pharmaceutical Press. pp. 665, 671. ISBN 9780857110848.
21. Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The
Australian Medicines Handbook Unit Trust. ISBN 9780980579093.
22. "Ibuprofen" (http://www.drugs.com/monograph/ibuprofen.html). The American Society
of HealthSystem Pharmacists. Retrieved 3 April 2011.\
23. Rao, P; Knaus, EE (20 September 2008). "Evolution of nonsteroidal anti-inflammatory
drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond.". Journal of Pharmacy
& Pharmaceutical Sciences. 11 (2): 81s–110s. PMID 19203472
(https://www.ncbi.nlm.nih.gov/pubmed/19203472).
21
24. "Ibuprofen: Pharmacology: Mechanism of Action. Updated on September 16, 2013"
(http://www.drugbank.ca/drugs/D B01050#). DrugBank, Open Data Drug & Drug
Target Database. Retrieved 24 July 2014.
25. Chan, LS (12 June 2014). Hall, R; Vinson, RP; Nunley, JR; Gelfand, JM; Elston, DM,
eds. "Bullous Pemphigoid Clinical Presentation"
(http://emedicine.medscape.com/article/1062391clinical# showall). Medscape
Reference. United States: WebMD.
26. Brayfield, A, ed. (14 January 2014). "Ibuprofen"
(http://www.medicinescomplete.com/mc/martindale/current/ms2657 h.htm).
Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press.
Retrieved 26 June 2014.
27. "The Synthesis of Ibuprofen" (http://www.rsc.org/learnchemistry/
resources/chemistryinyourcupboard/nurofen/6). Royal Society of Chemistry. Retrieved
14 November 2016.
28. Chen, CS; Shieh, WR; Lu, PH; Harriman, S; Chen, CY (12 July 1991). "Metabolic
stereoisomeric inversion of ibuprofen in mammals.". Biochimica et Biophysica Acta.
1078(3):411–7.doi:10.1016/01674838(91)90164U.PMID 1859831
(https://www.ncbi.nlm.nih.gov/pubmed/1859831).
29. Reichel, C; Brugger, R; Bang, H; Geisslinger, G; Brune, K (April 1997). "Molecular
cloning and expression of a 2arylpropionylcoenzyme A epimerase: a key enzyme in the
inversion metabolism of ibuprofen.". Molecular Pharmacology. 51 (4): 576–82. PMID
9106621 (https://www.ncbi.nlm.nih.gov/pubmed/9106621).
22
CHAPTER 2
LITERATURE REVIEW
23
2.1 Preparation of Silica gel by sol gel process:
The sol-gel technique has been used for reproduce new porous nanomaterials, with well-
defined structures and complex shapes. It is known that the sol-gel technology is relatively
simple and allows the control of the distribution of the components in molecules, through a
pre-orientation of the network. Thus, the potential applications of the materials synthesized by
this method can be competitive (also in terms of production costs). Sol-gel is a very flexible
route for the synthesis of inorganic, organic-inorganic networks such as glasses, ceramics,
films or powders. For a long time, sol-gel techniques have been used for manufacturing
glasses and ceramics, optical and electrical applications, medical science, protection coatings
and solar energy applications. The sol-gel process involves the formation of mineral phases
starting from soluble molecular precursors, following an inorganic polymerization reaction.
The reaction is at room temperature, in water or organic solvents and in a wide range of
pH/ionic strength conditions. The transition from a liquid (solution or colloidal solution) into a
solid (di- or multiphase gel) explains the name of the “sol-gel process”. The process involves
hydrolysis and condensation of metal alkoxides (Si(OR)4) such as tetraethylorthosilicate
(TEOS, Si(OC2H5)4) or inorganic salts such as sodium silicate (Na2SiO3) in the presence of
mineral acid (e.g., HCl) or base(e.g., NH3) as catalyst. A general flow chart for sol gel process
which leads to the production silica using silicon alkoxides (Si (OR) 4) is shown below.
The general reactions of TEOS that leads to the formation of silica particles in the sol-gel
process can be written as:
Si (OC2H5)4 + H2O HYDROLYSIS Si (OC2H5)3OH + C2H5OH
≡ Si − O −H + H− O − Si ≡ WATER CONDENSATION ≡ Si − O − Si ≡ + H2O
≡ Si − OC2H5 + H− O − Si ≡ ALCOHOL CONDENSATION ≡ Si − O − Si ≡ + C2H5OH

.
24
The hydrolysis of TEOS molecules forms silanol groups. The condensation / polymerization
between the silanol groups or between silanol groups and ethoxy groups create siloxane
bridges (Si–O–Si) that form entire silica structure.
2.1.1 Effect of parameter:
Catalyst:
In acid-catalyzed conditions, the hydrolysis kinetic is favored instead of the condensation,
which generally starts when hydrolysis is completed. In alkali-catalyzed reactions,
condensation is faster than hydrolysis, resulting in a highly condensed species that may
agglomerate into fine particles.
2.2 Silica gel as drug carrier:

Proper adsorption and entrapment of drug molecules in carrier granules leads to an
enhancement of physicochemical stability of the drug. The presence of larger number of
hydroxyl groups that form inter- and intra-molecular hydrogen bonded structure were
identified as a factor for enhancing dissolution. Adsorption is readily adoptable for thermo
labile drugs and carriers. Improved dissolution rates are attributed to decreased drug particle
size with a consequent increase in the surface area and to increase in the thermodynamic
activity of drug in dispersed state. Silica gel as drug carrier has following advantages [1]:
1. Rapid absorption due to bypassing of the liver and large surface area of respiratory.
2. Endothelium in inhalation route.
3. Rapid response and best bio-availability.
4. Liver is bypassed and hence the first pass effect is avoided, leading to improved.
5. Bioavailability.
6. Rapid absorption.
7. Drug stability is good due to neutral pH in the mouth.
8. Convenient, portable, easy to administer.
25
9. Pain free administration in oral routes.
10. No need for sterilization in oral routes.
11. Variety of dosages forms like fast release, slow release, enteric coating, etc. are
available.
12. In oral routes.
13. Local effects can be achieved by eye drops, ear drops, ointments, etc. in topical routes.
14. Easy to administer in transdermal.
15. Non - invasive in transdermal routes.
16. Patient compliance is high in transdermal routes.
17. Insulin less expensive.
18. Many of the medicines and remedies do not have negative side-effects.
2.3 Drug release:

Drug delivery refers to the way utilized to present the drug to the desired body site for drug
release and absorption.
2.3.1 Burst release:

Controlled drug delivery applications include both sustain delivery over days/weeks/months
and targeted delivery on a one-time or sustained basic. Normally short in duration, burst
release is worth through study due to high release rates that can be reached in the initial stage
after activation. The burst effect can be viewed from two perspectives: it is often regarded as a
negative consequence of creating long term controlled release devices or in certain situation,
rapid release or high initial rates of delivery may be desirable. Burst release may be the
optimal mechanism of delivery in several instances. One of the current difficulties with burst
release is that it is unpredictable and even when the burst is desired, the amount of burst can‟t
be significantly controlled.
26
Figure 2.1: graph shows the difference between Zero-order and burst release dosage forms.
2.3.2 Sustained release:

Sustained release dosage forms are designed to release a drug at a predetermined rate by
maintaining a constant drug level for a specific period of time with minimum side effects. In
the recent years, focus on the development of controlled release drug delivery systems has
increased. The basic rationale of controlled release drug delivery system optimizes the
biopharmaceutical, pharmacokinetic, and pharmacodynamics properties of a drug in such a
way that its utility is maximized, side-effects are reduced and cure or control of the condition
is achieved, in the shortest possible time by using smallest quantity of drug administered by
the most suitable route. There are several advantages of sustained release drug delivery over
conventional dosage forms like improved patient compliance due to less frequent drug
administration, reduction of fluctuation in steady-state drug levels, maximum utilization of
the drug, increased safety margin of potent drug, reduction in healthcare costs through
improved therapy, shorter treatment period and less frequency of dosing can be achieved.
27
This review briefly emphasizes about the sustained release drug delivery system
characteristics, formulation design and drug release mechanisms. Drug delivery system that
are designed to achieve prolonged therapeutic effect by continuously releasing medication
over an extended period of time after administration of single dose. The basic goal is achieve
steady state blood level that is therapeutically effective and nontoxic for an extended period of
time. Sustain release implies slow release of the drug over a time period. It may or may not be
controlled release. Drug should exhibit neither very fast rate of absorption nor excretions [2].
Figure 2.2: graph shows the difference between the conventional and sustained release dosage
forms.
28
2.3.3 Potential advantages and disadvantages of sustained release drug
forms:
Advantage:
1. The frequency of drug administration is reduced.
2. Patient compliance can be improved.
3. The total amount of drug administration can be reduced, thus
a) Maximizing availability with minimum dose.
b) Minimize drug accumulation with chronic dosing.
4. Improve efficacy in treatment,
a) Cure or control condition more promptly.
b) Improve/ control i.e. reduces-luctuation in drug level.
c) Improve bioavailability of some drugs.
d) Make use of special effect e.g. sustained release aspirin for morning relief of arthritis
by dosing before bed time.
5. Better control of drug absorption can be attained.
Disadvantages:
1. Reduced potential for dose adjustment.

2. Cost of single unit higher than conventional dosage forms.
3. Probability of dose dumping.
4. Increase potential for first pass metabolism.
5. Requirement for additional patient education for proper medication
6. Decreased systemic availability in comparison to immediate release conventional
dosage forms.
7. Administration of sustained release medication does not permit prompt termination of
therapy.
8. Flexibility in adjustment in dosage regimen is limited.
29
9. Controlled release forms are designed for normal population i.e., on the basis of
average drug biological half‐lives.
10. Economy factors may also be assessed, since most costly process and equipment are
involved in manufacturing so many controlled release dosage forms [3].
2.4 CHARACTERISTICS THAT MAKES DRUGS SUITABLE FOR

SUSTAINED RELEASE:
Absorption: The goal of forming a sustain release product is to control the release rate of
drug is much slower than the rate of absorption. If we presume that the transit time of most
drugs in the absorptive areas is about 8‐12 hours, the extreme half‐life for absorption should
be in the region of 3‐4 hours; otherwise, the dosage form will pass out of the probable
absorptive regions before drug release is complete. Thus corresponds to a minimum apparent
absorption rate constant of 0.17‐0.23 h-1 to give 80‐95% over this time period. So, it accepts
that the absorption of drug should occur at a relatively uniform rate over the entire length of
small intestine.
Distribution: The rate of elimination of drug is mainly depends upon the apparent volume of
distribution. So drugs with high apparent volume of distribution, influence the rate of
elimination of the drug, this drugs are consider to be a poor candidate for oral sustain release
drug delivery system.
Protein Binding: To achieve pharmacological response unbound drug concentration is

important rather than bound drug concentration and all drug bound to some extent to
plasma/tissue proteins. Protein binding of drug which shows a main role in its therapeutic
effect in spite of the type of dosage form as extensive binding to plasma increase biological
half‐life.
Molecular size and diffusivity: In several sustained release systems drug must diffuse
through a rate controlling membranes or matrix. Ability of a drug to diffuse through
30
membranes, it's so called diffusivity (diffusion coefficient), is a role of its molecular size. An
important influence upon the value of the diffusivity 'D' in silica gel is the molecular size for
molecular weight of the diffusing species [4].
2.5 There are several advantages of sustained release drug delivery over
conventional like burst release forms:
1. Improved patient compliance due to less frequent drug administration.
2. Reduction of fluctuation in steady-state drug levels.
3. Maximum utilization of the drug.
4. Increased safety margin of drug.
5. Reduction in healthcare costs through improved therapy.
6. Shorter treatment period [5].
2.6 Release kinetics:

There are number of kinetics models, which described the overall release of drug from the
dosage forms. Because qualitative and quantitative changes in a formulation may alter drug
release and in vivo performance, developing tools that facilitate product development by
reducing the necessity of bio-studies is always desirable. In this regard, the use of in vitro
drug dissolution data to predict in vivo bio-performance can be considered as the rational
development of controlled release formulation.
An in vitro dissolution study is carried out in SBF whose pH 7.0. The absorption of a drug
through the biological membrane depends on the amount of drug available at the absorption
site. This intern is dependent on the route of drug release from the delivery device. The
mechanism of drug release can be approximated by fitting the dissolution data in different
kinetic models. The results obtained from in vitro release studies is plotted in different models
according to zero order (cumulative amount of drug release versus time), first-order (log
cumulative percentage of drug remaining versus time), Higuchi (cumulative percentage of
31
release versus square root of time), and Korsmeyer-Peppas (log cumulative percentage of drug
released versus log time) equation models [46].
To find out the kinetics of drug release from matrices, the dissolution data obtained from each
experiment treated with different kinetic release equations [6]. The release data were plotted
according to following model dependent methods equation:
Zero order:
Qt =Q0 – kt (2.1)
First order:
- (2.2)
Higuchi model:
√ (2.4)
Korsmeyer-Peppas model:
(2.5)
Where M,C and Q is the amount of drug released at time t, Mₒ and Cₒ is total amount of drug
and Kₒ, Kt and k are corresponding rate constant.
The above equations are mathematical model to study release kinetics.
Model dependent methods are based on different mathematical functions, which describe the
dissolution profile. Once a suitable function has been selected, the dissolution profiles are
evaluated depending on the derived model parameters. In order to determine the suitable drug
release kinetic model describing the dissolution profile, the nonlinear regression module of
statistica 5.0 was used. In non-linear regression analysis the Quasi-Newton and Simplex
methods minimized the least squares [7].
2.6.1 Zero-order model:

Drug dissolution from dosage forms that don‟t disaggregate and release the drug slowly can
be represented by the equation:
32
Q0 - Qt = k0t (2.5)
Rearrangement of equation (2.5) yields:
Qt = Q0 + k0t (2.6)
In equation (2.6) Qt is the amount of drug dissolved in time t, Q0 is the initial amount of drug
in the solution (most times, Q0=0) and K0 is the zero order release constant expressed in units
of concentration/time.
To study the release kinetics, data obtained from in vitro drug release studies were plotted as
Cumulative amount of drug released versus time [8] [9].
Application: This relationship can be used to describe the drug dissolution of several types of
modified release pharmaceutical dosage forms, as in the case of some transdermal systems, as
well as matrix tablets with low soluble drugs in coated forms, osmotic systems, etc. [10][11].
2.6.2 First order:

This model has also been used to describe absorption and/or elimination of some drugs,
although it is difficult to conceptualize this mechanism on a theoretical basis. The release of
the drug which followed first order kinetics can be expressed by the equation:
= - kc (2.7)
Where K is first order rate constant expressed in units of time-1.

Equation (2.7) can be expressed as:
- (2.8)
Where in equation (2.8) C0 is the initial concentration of drug, K is the first order rate
constant, and t is the time [12]. The data obtained are plotted as log cumulative percentage of
drug remaining vs. time which would yield a straight line [13] with a slope of -K/2.303.
33
Application: This relationship can be used to describe the drug dissolution in pharmaceutical
dosage forms such as those containing water-soluble drugs in porous matrices.
2.6.3 Higuchi model:

The first example of a mathematical model aimed to describe drug release from a matrix
system was proposed by Huguchi in 1961 [14]. Initially conceived for planar systems, it was
then extended to different geometrics and porous systems [15]. This model is based on the
hypotheses that (i) initial drug concentration in the matrix is much higher than drug solubility;
(ii) drug diffusion takes place only in one dimension (edge effect must be negligible); (iii)
drug particles are much smaller than system thickness; (iv) matrix swelling and dissolution are
negligible; (v) drug diffusivity is constant; and (vi) perfect sink conditions are always attained
in the release environment. Accordingly, model expression is given by the equation:
ft = Q = A√ ( ) (2.9)
Where Q is the amount of drug released in time t per unit area A, C is the drug initial
concentration, Cs is the drug solubility in the matrix media and D is the Diffusivity of the
drug molecules (diffusion coefficient) in the matrix substance. This relation is valid during all
the time, except when the total depletion of the drug in the therapeutic system is achieved. To
study the dissolution from a planar heterogeneous matrix system, where the drug
concentration in the matrix is lower than its solubility and the release occurs through pores in
the matrix, the expression is given by equation:
ft = Q = √ ( ) (2.10)
where D is the diffusion coefficient of the drug molecule in the solvent, δ is the porosity of the
matrix, is the tortuosity of the matrix and Q, A, Cs and t have the meaning assigned above.
Tortuisity is defined as the dimensions of radius and branching of the pores and canals in the
34
matrix. In a general way it is possible to simplify the Higuchi model (31) as (generally known
as the simplified Higuchi model):
√ (2.11)
Where, KH is the Higuchi dissolution constant [16]. The data obtained were plotted as
cumulative percentage drug release versus square root of time [17-18] .
Application: This relationship can be used to describe the drug dissolution from several types
of modified release pharmaceutical dosage forms, as in the case of some transdermal systems
and matrix tablets with water soluble drugs [19].
2.6.4 Korsmeyer-Peppas model:

Korsmeyer (1983) derived a simple relationship which described drug release from a
polymeric system equation. To find out the mechanism of drug release, first 60% drug release
data were fitted in Korsmeyer- Peppas model [20]
(2.12)
Where Mt / M∞ is a fraction of drug released at time t, k is the release rate constant and n is
the release exponent. The n value is used to characterize different release for cylindrical
shaped matrices. In this model, the value of n characterizes the release mechanism of drug as
described in Table 1.
Release exponent (n) Drug transport Rate as a function of

mechanism time
n=0.5 Fickian diffusion t-.5

0.45 < n < 0.89 Non- Fickian transport tn-1
n= 0.89 case II transport Zero order release
n>0.89 Super case II transport tn-1
35
For the case of cylindrical tablets, 0.45 ≤ n corresponds to a Fickian diffusion mechanism,
0.45 < n <0.89 to non-wFickian transport, n = 0.89 to Case II (relaxation) transport, and n >
0.89 to super case II transport [21]. To find out the exponent of n the portion of the release
curve, where Mt / M∞ < 0.6 should only be used. To study the release kinetics, data obtained
from in vitro drug release studies were plotted as log cumulative percentage drug release
versus log time.
2.7 Different type of analgesic: We all suffer from some kind of physical pain in our
daily lives and to overcome that pain we end up eating pain killers which are actually
analgesics. Analgesics reduce the effect of pain without causing any mental confusion,
paralysis or any other disturbances in the nervous system, so that you actually get rid of the
pain without any imbalance in the nervous system. The analgesic drugs can act in many ways
on the peripheral or central nervous system, but they do not eliminate the sensation of pain as
in the case of anesthetics. Analgesics can be broadly classified into two categories:
2.7.1 The non-narcotic (non-addictive) analgesics: This type of drug is generally used for
relieving the skeleton pain which can happen due to arthritis. Ibrufen, Aspirin and
paracetamol are the most common drugs in this case. When you take aspirin, it acts by
inhibiting the synthesis of the chemical known as prostaglandins by chemical reactions which
causes inflammation in the tissues and as a result the sensation of pain is felt. These drugs
also help in reducing fever and prevent the platelet coagulation. The anti-blood clotting action
is the reason why aspirin is used for the prevention of heart attacks.
2.7.2 The narcotic analgesic: These types of analgesic drugs are taken for medical use in
prescribed doses, where they act by relieving the pain and producing sleep. If the dose of this
analgesic drug increases then it can lead to coma, convulsion and finally result in death.
Morphine is the most common type of narcotic analgesic used nowadays; they are also
referred to as opiates since they are obtained from opium poppy. The narcotic analgesics or
pain killers are mostly used for reliving postoperative pain, cardiac pain and the pain of
terminal cancer [22].
36
2.8 General drug delivery:
Drug medicine is still the medicine of choice for three-quarters of the Earth‟s population. The
basic principles of natural healing in particular, is that man is a part of nature and can, if given
the right encouragement and support, heal himself. He can do this both emotionally and
physically using the principles of right living and the use of mild drugs and raw foods. We
also need to balance ourselves through diet, exercise, mental and emotional attitudes and
experiences, which are called "freedom of the spirit." We need to ." We need to balance health
first through proper nutrition with the help of drug serving as special foods for both body and
mind. African people are able to absorb more stimuli and utilize nutrients better, which brings
Africans closer in harmony with nature. . There can be no true healing with drugs if the diet
remains the contributing cause in sustaining the disease [23].
Drug delivery alludes to approaches, formulations, innovations, technologies, and systems for
incorporating a pharmaceutical compound in the body system. It needed to safely achieve its
desired therapeutic effect. It may involve scientific site targeting within the body. It might
involve systemic pharmacokinetics. It is typically concerned with both quantity and duration
of drug presence. Drug delivery is often approached via a drug‟s chemical formulation, but it
may also involve medical devices or drug-device combination products [24].
Drug delivery is a concept heavily integrated with dosage form and route of administration,
the latter sometimes even being considered part of the definition. Drug delivery technologies
modify drug release profile, absorption, distribution and elimination for the benefit of
improving product efficacy and safety, as well as patient convenience and compliance. Drug
release is from: diffusion, degradation, swelling, and affinity-based mechanisms. Most
common routes of administration include the preferred non-invasive per oral (through the
mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and rectal) and
inhalation routes. Many medications such as peptide and protein, antibody, vaccine and gene
based drugs, in general may not be delivered using these routes because they might be
susceptible to enzymatic degradation or cannot be absorbed into the systemic circulation
efficiently due to molecular size and charge issues to be therapeutically effective. For this
37
reason many protein and peptide drugs have to be delivered by injection or a nano-needle
array. For example, many immunizations are based on the delivery of protein drugs and are
often done by injection [25].
In the area of drug delivery current efforts include the development of targeted delivery where
the drug is only major active in the target area of the body (for example, in cancerous tissues),
sustained release formulations in which the drug is released over a period of time in a
controlled manner from a formulation, and methods to increase survival of per oral agents
which must pass through the stomach‟s acidic environment. In order to achieve efficient
targeted delivery, the designed system must avoid the host‟s defense mechanisms and
circulate to its intended site of action [26].
We must introduce high quality foods in place of a lower quality diet in our bodies. This
principle applies to all our major food groups. As we go higher on the scale of quality, the
closer-food comes in the natural state in which it occurs; whole raw and unrefined. In this
condition, all enzymes are found intact. Amino acids are in their finest form. The minerals,
proteins, hormones, vitamins, trace elements and carbohydrates capable of reproducing
healthy tissue are present. When an individual makes a conscious choice to use natural herbs
and foods to heal themselves, it encourages a respect for harmonizing one‟s self with nature
and the universal forces. This is the plan of nature [27].
38
REFRENCES
1. “Current Project. “King‟s College London. http://www.kcl.ac.uk.

2. SUSTAINED RELEASE DRUG DELIVERY SYSTEM: A CONCISE REVIEW, LILESH
KHALANE , ATUL ALKUNTE, ARUNADEVI BIRAJDAR (Adarsh Shikshan Prasarak
Mandal‟s, K. T. Patil college of Pharmacy).
3. Sustained Release Drug Delivery System: A Modern Formulation Approach Pooja R.
Alli, Pratima B. Bargaje Nilesh S. Mhaske.
4. Asian Journal of Pharmaceutical Technology and Innovation Sustained Release Drug
Delivery System: A Modern Formulation Approach Pooja R. Alli*, Pratima B.
Bargaje*, Nilesh S. Mhaske.
5. Bao Chen, Guilan Quan, Zhouhua Wang, Jianwen Chen, Linna Wu, Yuehong Xu.
"Hollow mesoporous silica‟s as a drug solution delivery system for insoluble drugs."
Powder Technology Vol 240 (2013): 48–53
6. Costa P., Lobo J.M.S.: Eur. J. Pharm. Sci., 13,123 (2001).
7. Freitas M.N., Marchetti J.M.: Int. J. Pharm. 295, 201 (2005).
8. Release kinetics, data interpretation. in: Encyclopedia of Controlled Drug Delivery.
Narashimhan B., Mallapragada S.K., Peppas N.A. Eds., p. 921, John Wiley and Sons,
Inc., New York 1999.
9. Quantitative calculations in pharmaceutical practice and research. Hadjiioannou T.P.,
Christian G.D., Koupparis MA. Eds., VCH Publishers Inc., New York 1993.
10. Libo Y., Reza F.: J. Pharm. Sci. 85, 170 (1996).
11. Freitas M.N., Marchetti J.M.: Int. J. Pharm. 295, 201 (2005).
12. Narashimhan B., Mallapragada S.K., Peppas, N.A.: Release kinetics, data
interpretation, in: Encyclopedia of controlled drug delivery, Mathiowitz E. Ed., John
Wiley and Sons, Inc., New York 1999.
13. Silvina A., Bravo M., Lamas C., Claudio J.: J. Pharm. Pharm. Sci. 5, 213 (2002).
14. Higuchi T.: J. Pharm. Sci. 84, 1464 (1963).
15. Grassi M., Grassi G.: Curr. Drug Deliv. 2, 97 (2005).
16. Arhewoh M.I., Okhamafe O.A.: J. Med. Biomed. Res. 3, 7 (2004).
39
17. Higuchi T.: J. Pharm. Sci. 84, 1464 (1963).
18. Grassi M., Grassi G.: Curr. Drug Deliv. 2, 97 (2005)
19. Shoaib H.M., Tazeen J., Merchant A.H., Yousuf I.R.: Pak. J. Pharm. Sci. 19, 119
(2006).
20. Riger P.L, Peppas N.A.: J. Control. Rel. 5, 37 (1987).
21. Siepmann J., Peppas N.A.: Adv. Drug Deliv. Rev. 48, 139 (2001).
22. http://byjus.com/chemistry/analgesics-analgesic-drugs-classification/
23. “Drug Delivery Systems (definition)".
24. “Drug delivery - definition of drug delivery by Medical dictionary”.
TheFreeDictionary.com.
25. Wang, NX; von Recum, HA (2011). “AffinityBased Drug Delivery”. Macromol
Biosci 11:321–332. doi:10.1002/mabi.201000206.
26. “Definition”. Retrieved 2008-05-27.
27. “Definition”. Retrieved 2008-05-27.
40
CHAPTER 3
OBJECTIVE
41
OBJECTIVE
The major Objective of this project are given as under -
a) Silica gel is synthesized by using TEOS: ETOH: DI WATER in 1:2:1
and 1:2:2 ratios by sol gel process.
b) Entrapment of Ibrufen in mesoporous Silica gel to study the release of
Ibrufen in Simulated Body Fluid (SBF).
c) Characterization of Ibrufen entrapped silica gel using XRD, FTIR &
FESEM.
d) Study of burst and sustained release kinetics of Ibrufen in Simulated
Body Fluid (SBF) using UV-Vis spectroscopy.
42
CHAPTER 4
METHODLOGY
43
4.1 The methodology is followed:
1) Silica gel is synthesized using Tetra Ethyl Ortho Silicate (TEOS), Ethyl alcohol (ETOH)
and DI Water as a precursor in the ratio TEOS: DI WATER: ETOH =1:2:1and 1:2:2.
2) Silica gel is characterized using XRD and FESEM. From XRD the phases of the sample
are revealed and from FESEM analysis the morphology of silica gel is found. Ibrufen is
procured in solid and liquid form from market.
3) Entrapment of Ibrufen in the Silica gel matrix is carried out at room temperature and
characterized by FTIR.
4) Simulated Body Fluid of pH 7.0 is prepared.
5) Release of silica gel entrapped Ibrufen is carried out in SBF using UV-Vis.
6) The kinetic study of release mechanism is analyzed.
The detailed method is shown in flowchart.
44
4.2 Entrapment of Ibrufen with Silica gel matrix of TEOS: ETOH: DI
WATER:
Drop wise added

Ibrufen + TEOS + C2H5OH DI WATER + C2H5OH
Stirring at room temperature
Silica sol with Ibrufen
Drying at room temperature for 7 days
Silica gel with entrapped

Ibrufen
Characterization using XRD,

FTIR, FESEM
Silica gel dissolved in SBF
Flow chart 1: Methodology followed for one synthesis of Ibrufen entrapped silica gel and
release of Ibrufen in SBF.
45
4.3 Characterization of Silica gel using XRD, FTIR, FESEM:
4.3.1 XRD:
Phase identification of the synthesized samples were analyzed by X-ray diffractometer
(Rigaku Ultima III) with CuKα radiation (λ = 0.15418 nm) in a continuous scan mode from
10° to 80° was used to record the data. The scan speed is maintained at 50/minute.
4.3.2 FTIR:
Fourier transformed spectra of the synthesized samples were taken by Fourier transform
infrared spectrophotometer (Shimadzu IR Prestige, Japan) in the wavenumber range 400 -
4500 cm-1. FTIR study of the samples was carried out to check the bonds present in the silica
gel, Ibrufen and in the Ibrufen entrapped silica gel.
4.3.3 UV-Vis Spectroscopy:

Deuterium discharge lamps are used as a source for characterization in UV region (190-400
nm) and a tungsten-halogen lamp is used for visible and near IR characterization (300-
2500nm) to study the intensity of the drug released in SBF for the kinetic analysis.
4.4 Preparation of Simulated body Fluid formation:

750ml of ultra-pure (DI) water was taken and ingredients were measured in an electronic
weighing machine with added water by the use of magnetic stirrer one by one according the
table. At last pH of SBF was measured 7.0.
46
Reagents SBF for 1litre
(wt.in gram)
NaCl 7.996
NaHCO3 0.35
KCl 0.224
K2HPO4 .3H2O 0.228
MgCl2.6H2O 0.305
1 Kmol/mᵌ HCl 40 cmᵌ
CaCl2 0.278
Na2SO4 0.071
(CH2OH)3CNH2 6.057
Ultra-Pure water 750ml
Table 4.1: Composition of SBF
4.5 Study of Release Mechanism:
4.5.1 Burst release:

Silica gel containing solid/liquid Ibrufen was dipped in 20ml of simulated body fluid (SBF)
and kept in the orbital shaking incubator. After 15 min, 30 min, 45 min, 1hour, 2 hour, 3 hour,
4 hour, 5 hour & 6 hour, 3ml of solution was taken from the beaker and 3ml of fresh SBF was
added into the solution.
4.5.2 Sustained release:

Silica gel containing solid/liquid Ibrufen was dipped in 20ml of simulated body fluid (SBF)
and kept in the orbital shaking incubator. After 24 hour, 48 hour, 72 hour, 96 hour, 120 hour,
144 hour & 168 hour, 3ml of solution was taken from the beaker and 3ml of fresh SBF was
added into the solution.
47
CHAPTER 5
Characterization
TECHNIQUES
48
5.1 X-Ray Powder Diffraction analysis:
X-ray powder diffraction (XRD) is a rapid analytical technique primarily used for phase
identification of a crystalline material and can provide information on unit cell dimensions.
The analyzed material is finely ground, homogenized, and average bulk composition is
determined [1].
5.1.1 Fundamental principle of XRD:
Crystalline substances act as three-dimensional diffraction gratings for X-ray wavelengths

similar to the spacing of planes in a crystal lattice. X-ray diffraction is now a common
technique for the study of crystal structures and atomic spacing.
X-ray diffraction is based on constructive interference (i.e., in phase) of monochromatic X-

rays and a crystalline sample. These X-rays are generated by a cathode ray tube, filtered to
produce monochromatic radiation, collimated to concentrate, and directed toward the sample.
The interaction of the incident rays with the sample produces constructive interference (and a
diffracted ray) when conditions satisfy:
Bragg's Law:
nλ = 2d sin θ (5.1)
Equation (5.1) relates the wavelength of electromagnetic radiation to the diffraction angle and
the lattice spacing in a crystalline sample. These diffracted X-rays are then detected, processed
and counted. By scanning the sample through a range of 2θangles, all possible diffraction
directions of the lattice should be attained due to the random orientation of the powdered
material. Conversion of the diffraction peaks to d-spacing allows identification of the mineral
because each mineral has a set of unique d-spacing. Typically, this is achieved by comparison
of d-spacing with standard reference patterns [2].
49
All diffraction methods are based on generation of X-rays in an X-ray tube. These X-rays are
directed at the sample, and the diffracted rays are collected. A key component of all
diffraction is the angle between the incident and diffracted rays. Powder and single crystal
diffraction vary in instrumentation beyond this.
5.1.2 Production of X-RAY:
Figure 5.1: schematic diagram of X-RAY.
X-ray diffractometers consist of three basic elements: an X-ray tube, a sample holder, and an
X-ray detector. X-rays are generated in a cathode ray tube by heating a filament to produce
electrons, accelerating the electrons toward a target by applying a voltage, and bombarding the
target material with electrons [3].
50
When electrons have sufficient energy to dislodge inner shell electrons of the target material,
characteristic X-ray spectra are produced. These spectra consist of several components, the
most common being Kα and Kβ. Kα consists, in part, of Kα1 and Kα2. Kα1 has a slightly shorter
wavelength and twice the intensity as Kα2. The specific wavelengths are characteristic of the
target material (Cu, Fe, Mo, and Cr). Filtering, by foils or crystal monochromators, is required
to produce monochromatic X-rays needed for diffraction. Kα1and Kα2 are sufficiently close in
wavelength such that a weighted average of the two is used. Copper is the most common
target material for single-crystal diffraction, with CuKα radiation λ = 1.5418Å. These X-rays
are collimated and directed onto the sample.
As the sample and detector are rotated, the intensity of the reflected X-rays is recorded. When
the geometry of the incident X-rays impinging the sample satisfies the Bragg Equation,
constructive interference occurs and a peak in intensity occurs. A detector records and
processes this X-ray signal and converts the signal to a count rate which is then output to a
device such as a printer or computer monitor. The geometry of an X-ray diffractometer is such
that the sample rotates in the path of the collimated X-ray beam at an angle θ while the X-ray
detector is mounted on an arm to collect the diffracted X-rays and rotates at an angle of 2θ.
The instrument used to maintain the angle and rotate the sample is termed a goniometer. For
typical powder patterns, data is collected at 2θ from ~5° to 70°; angles that are preset in the X-
ray scan [4].
5.1.3 Importance of X-RAY:
 Measure the average spacing between layers or rows of atoms.
 Determine the orientation of a single crystal or grain.
 Find the crystal structure of an unknown material.
 Measurement the size, shape and internal stress of small crystalline region.
51
5.1.4 Determination of interplanar spacing:
Diffraction occurs only when Bragg‟s Law is satisfied Condition for constructive interference
(X-RAY) from planes with spacing d. The inter planer spacing calculated from Bragg‟s Law
equation [5].
Bragg’s Law:
nλ = 2dhklSinθ (5.2)
Figure 5.2: Inter planar spacing diagram of particles.
Where
n = any integer.
λ = The X-RAY wavelength.
θ = Bragg‟s angle.
d = the inter-planer spacing.
52
5.1.5 Determination of particle size or grain size:
Fig 5.3: schematic diagram of an X-RAY diffraction peak to measure the FWHM.
The mean crystalline sizes of the powders are calculated using Scherrer’s formula
D= (5.3)
In equation (3) D is them average crystallite size, λ =1.541 A° (X-ray wavelength),

β = √( ) being the width of the diffraction peak at half maximum for the diffraction
angle 2θ, b is calculated from the peak width of single crystal silicon wafer [6].
5.1.6 Phase identification:
 Measure d-spacing from the obtained XRD pattern.
 Obtain integrated intensities.
53
 Compare data with known standards in the JCPDS file, which are for random
orientations.
 There are more than 50,000 JCPDS cards of inorganic materials [7].
Figure 5.4: Photograph of Rigaku Ultima III X-ray Diffractometer.
54
5.2 UV-Vis Spectrophotometer analysis:
Ultraviolet–visible spectroscopy or ultraviolet-visible spectrophotometry (UV-Vis or UV/Vis)
refers to absorption spectroscopy or reflectance spectroscopy in the ultraviolet-visible spectral
region. Ultraviolet and visible (UV-Vis) absorption spectroscopy is the measurement of the
attenuation of a beam of light after it passes through a sample or reflect from a sample surface.
Absorption measurement can be at a single wavelength or over an extended spectral range.
5.2.1 Principle of UV spectroscopy:
UV spectroscopy obeys the Beer-Lambert law, which states that: when a beam of
monochromatic light is passed through a solution of an absorbing substance, the rate of
decrease of intensity of radiation with thickness of the absorbing solution is proportional to
the incident radiation as well as the concentration of the solution.
The expression of Beer-Lambert law is given below as:
A = log10 (I0/I) = εcL (5.4)
Where, A = absorbance, in Absorbance Units (AU).
I/I0 = transmittance.
I0 = intensity of incident light at a given wavelength.
I = intensity of light leaving sample cell.
c = molar concentration of absorbing species.
L = path length of sample cell (cm.).
ε = molar absorptivity or extinction coefficient.
From the Beer-Lambert law it is clear that greater the number of molecules capable of
55
absorbing light of a given wavelength, the greater the extent of light absorption. This is the
basic principle of UV spectroscopy.
5.2.2 Basic component for measuring wavelengths:
Light source:
Tungsten filament lamps and Hydrogen-Deuterium lamps are most widely used and suitable
light source as they cover the whole UV region. Tungsten filament lamps are rich in red
radiations; more specifically they emit the radiations of 375 nm, while the intensity of
Hydrogen-Deuterium lamps falls below 375 nm.
Monochromator:
Monochromators generally composed of prisms and slits. The most of the spectrophotometers
are double beam spectrophotometers. The radiation emitted from the primary source is
dispersed with the help of rotating prisms. The various wavelengths of the light source which
are separated by the prism are then selected by the slits such the rotation of the prism results in
a series of continuously increasing wavelength to pass through the slits for recording purpose.
The beam selected by the slit is monochromatic and further divided into two beams with the
help of another prism.
Sample and reference cells:
One of the two divided beams is passed through the sample solution and second beam is passé
through the reference solution. Both sample and reference solution are contained in the cells.
These cells are made of either silica or quartz. Glass can't be used for the cells as it also
absorbs light in the UV region.
Detector: Generally two photocells serve the purpose of detector in UV spectroscopy. One
of the photocell receives the beam from sample cell and second detector receives the beam
from the reference. The intensity of the radiation from the reference cell is stronger than the
56
beam of sample cell. This results in the generation of pulsating or alternating currents in the
photocells.
Amplifier:
The alternating current generated in the photocells is transferred to the amplifier. The
amplifier is coupled to a small servometer. Generally current generated in the photocells is of
very low intensity, the main purpose of amplifier is to amplify the signals many times so we
can get clear and recordable signals.
Recording devices:
Most of the time amplifier is coupled to a pen recorder which is connected to the computer.
Computer stores all the data generated and produces the spectrum of the desired compound
[8].
Figure 5.5: Basic diagram of UV-Vis spectrophotometer.
The basic parts of a spectrophotometer are a light source, a holder for the sample, a diffraction
grating in a monochromator or a prism to separate the different wavelengths of light, and a
detector. The radiation source is often a Tungsten filament (300-2500 nm), a deuterium arc
57
lamp, which is continuous over the ultraviolet region (190-400 nm), Xenon arc lamp, which is
continuous from 160-2,000 nm; or more recently, light emitting diodes (LED) for the visible
wavelengths. The detector is typically a photomultiplier tube, a photodiode, a photodiode
array or a charge-coupled device (CCD). Single photodiode detectors and photomultiplier
tubes are used with scanning monochromators, which filter the light so that only light of a
single wavelength reaches the detector at one time. The scanning monochromator moves the
diffraction grating to "step-through" each wavelength so that its intensity may be measured as
a function of wavelength. Fixed monochromators are used with CCDs and photodiode arrays.
As both of these devices consist of many detectors grouped into one or two dimensional
arrays, they are able to collect light of different wavelengths on different pixels or groups of
pixels simultaneously [9].
5.3 FTIR (Fourier Transform Infrared Spectroscopy) analysis:
FT-IR stands for Fourier Transform Infra-Red, the preferred method of infrared spectroscopy.
In Infra-red spectroscopy, IR radiation is passed through a sample. Some of the infrared
radiation is absorbed by the sample and some of it is passed through transmitted. The resulting
spectrum represents the molecular absorption and transmission, creating a molecular finger
print of the sample. Like a fingerprint no two unique molecular structures produce the same
infrared spectrum. Fourier Transform Infrared Spectroscopy (FTIR) is a technique which is
used to broad analyze the chemical composition of many organic chemicals, polymers, paints,
coatings, adhesives, lubricants, semiconductor materials, coolants, gases, biological samples,
inorganics and minerals. This makes infrared spectroscopy useful for several types of analysis.
FTIR can be used to analyze a wide range of materials in bulk or thin films, liquids, solids,
pastes, powders, fibers, and other forms. FTIR analysis not only gives qualitative
(identification) analysis of materials, but with relevant standards, can be used for quantitative
(amount) analysis. FTIR can be used to analyze samples up to ~11millimeters in diameter. It
either measure in bulk or the top ~1 micrometer layer. An FTIR Spectrometer is an instrument
which acquires broadband NIR to FIR spectra. Unlike a dispersive instrument, i.e. grating
mono-chromator or spectrograph, a FTIR Spectrometer collects all wavelengths
58
simultaneously. FT-IR (Fourier Transform Infra-Red) is a method of obtaining infrared
spectra by first collecting an interferogram of a sample signal using an interferometer, and
then performing a Fourier Transform (FT) on the interferogram to obtain the spectrum. An
FTIR Spectrometer collects and digitizes the interferogram, performs the FT function, and
displays the spectrum. FT-IR spectroscopy covers both the basic theory of FT-IR and how it
works as well as discussing some the practical aspects of FT-IR use [10].
5.3.1 Principle of operation:

FTIR is typically based on a Michelson Interferometer. The interferometer consists of abeam
splitter, a fixed mirror, and a mirror that translates back and forth, very precisely. The beam
splitter is made of a special material that transmits half of the radiation striking it and reflects
the other half. Radiation from the source strikes the beam splitter and separates into two
beams. One beam is transmitted through the beam splitter to the fixed mirror and the second is
reflected off the beam splitter to the moving mirror. The fixed and moving mirrors reflect the
radiation back to the beam splitter. Again, half of this reflected radiation is transmitted and
half is reflected at the beam splitter, resulting in one beam passing to the detector and the
second back to the source.
Figure 5.6: Schematic diagram of FTIR.
59
A beam of infrared light (wavelength ~ 0.7-500 μm) is focused on the sample using all
reflective optics. Depending on the sample composition, differing amounts of light are
absorbed a different wavelengths. This pattern of light absorption is unique for almost every
organic compound (except optical isomers) and many inorganic compounds. From the pattern
of light absorbed, identification of the composition (qualitative analysis) can be made. With
additional control over the sample thickness or sampling depth, the intensity of the individual
absorbing components can be used to perform quantitative analysis (amount of each
compound present) [3]. User-provided reference samples aid in positive substance
identification and compositional verification. FTIR can be used to identify chemicals from
spills, paints, polymers, coatings, drugs, and contaminants. FTIR is the most powerful
instrument for identifying types of chemical bonds (functional groups). The wavelength of
light absorbed is characteristic of the chemical bond a scan be seen in this annotated spectrum.
A Shimadzu IRPrestige-21 FTIR spectrometer was used to record the spectra in the mid IR
region, (i.e. 400 – 4000 cm−1) as shown in figure below.
Figure 5.7: Photograph of Shimadzu IRPrestige-21 FTIR spectrometer.
60
So, we got the information from FT-IR
 It can identify unknown materials from their different bonds.

 It can determine the quality or consistency of a sample.
 It can determine the amount of components in a mixture.
There are three modes:
Those modes are absorption, transmittance and reflectance. Specifically to calculate optical
constant near IR region, have to use FTIR reflectance mode.
 Internal Reflection Spectroscopy: Attenuated Total Reflection (ATR).
 External Reflection Spectroscopy: Specular Reflection (smooth surfaces).
 Combination of Internal and External Reflection: Diffuse Reflection (DRIFTs) (rough
surfaces).
5.4 FIELD EMISSION SCANNING ELECTRON MICROSCOPY:
A FESEM that works with electrons (particles with negative charge) instead of light. The
electrons are liberated by a field emission source commonly known as cold cathode. It is
basically a low voltage device working on Field emission rather than Thermionic emission.
The object is scanned by electrons according to a zigzag pattern.
5.4.1 Principle of FESEM:

A FESEM is used to visualize very small topographic details on the surface or entire
fractioned objects. Under vacuum, electrons are generated either by a low voltage source (cold
cathode) or Field Emission Source in case of FESEM or a thermionic source in case of a
SEM, are accelerated in a field gradient. The beam passes through Electromagnetic Lenses,
focusing onto the specimen. As result of this bombardment different types of electrons are
61
emitted from the specimen. The angle and velocity of these electrons relates to the surface
structure of the object. A detector catches the secondary electrons and an image of the sample
surface is constructed by comparing the intensity of these secondary electrons to the scanning
primary electron beam. Finally, the image displayed on a monitor is saved and processed
further.
5.4.2 Components of a typical FESEM:
The main components are illustrated as follows:
 Electron column with lenses and apertures.

 Scanning system.
 Detector(s).
 Display.
 Vacuum system.
 Electronics controls.
Figure 5.8: Components of FESEM
62
In this experiment Hitachi S-4800 equipped with energy dispersive x-ray (EDAX) was
utilized to examine the surface morphology.
Fig.5.9. Field emission scanning electron microscopy (FESEM) coupled with EDAX (Hitachi
S-4800).
63
REFERENCES
1. http://serc.carleton.edu/research_education/geochemsheets/techniques/XRD.html
2. Bish, DL and Post, JE, editors. 1989. Modern Powder Diffraction. Reviews in
Mienralogy, v. 20. Mineralogical Society of America.
3. Cullity, B. D. 1978. Elements of X-ray diffraction. 2nd ed. Addison-Wesley, Reading,
Mass.
4. Klug, H. P., and L. E. Alexander. 1974. X-ray diffraction procedures for
polycrystalline and amorphous materials. 2nd ed. Wiley, New York.
5. Moore, D. M. and R. C. Reynolds, Jr. 1997. X-Ray diffraction and the identification
and analysis of clay minerals. 2nd Ed. Oxford University Press, New York.
6. Hanno zur Loye, X-Ray Diffraction HOW IT WORKS WHAT IT CAN AND WHAT
IT CANNOT TELL US.
7. Hanno zur Loye, X-Ray Diffraction HOW IT WORKS WHAT IT CAN AND WHAT
IT CANNOT TELL US.
8. http://www.indiastudychannel.com/resources/146681-Principle-working-and-
applications-of-UV-spectroscopy.aspx
9. https://en.wikipedia.org/wiki/Ultraviolet–visible_spectroscopy
10. Road • Madison, WI 53711-4495 • U.S.A., E-MAIL: nicinfo@thermonicolet.com •
www.thermonicolet.com
64
CHAPTER 6
RESULT & DISCUSSION
65
6.1 Characterization of Silica gel using XRD:
6.1.1 XRD analysis:
Figure 6.1(a) & 6.1(b) represents the XRD pattern of bare silica gel in two
different ratio e.g., TEOS: ETOH: DI WATER (1ml: 2ml: 1ml) & TEOS: ETOH: DI WATER
(1ml: 2ml: 2ml). We get that there is a hump in between 150-250 at room temperature which
indicates the presence of amorphous silica. There is no other peak is present, which indicates
pure amorphous silica.
Figure 6.1(a): XRD pattern of bare silica gel in TEOS: ETOH: DI WATER (1:2:1) ratio.
66
Figure 6.1(b): XRD pattern of bare silica gel in TEOS: ETOH: DI WATER (1:2:2) ratio
67
6.2 FESEM analysis:
Figure 6.12 (a) & 6.12 (b) shows the FESEM of bare silica gel in two different ratios.
Figure 6.12(a)
Figure 6.12(b)
Figure 6.12(a) & (b): FESEM of bare silica gel of TEOS: ETOH: DI WATER in (1:2:1) ratio.
68
Figure 6.13(a)
Figure 6.13(b)
Figure 6.13(a) & (b): FESEM of bare silica gel of TEOS: ETOH: DI WATER in (1:2:2) ratio
69
6.3 FTIR analysis:
Characterizations of the samples are carried out using FTIR. The Fourier transform infrared
(FTIR) spectrum of the bare silica gel, Ibrufen and silica gel-entrapped Ibrufen is taken using
an FTIR spectroscope.
6.3.1 Solid Ibrufen entrapped in Silica gel matrix of TEOS: ETOH: DI

WATER (1:2:1) ratio:
Figure 6.2(a): FTIR of Solid Ibrufen entrapped with silica gel matrix of TEOS: ETOH: DI
WATER (1:2:1) ratio.
70
Bare Solid Silica gel
silica gel Ibrufen entrapped
1:2:1 Ibrufen
Wavenumber Vibration Wavenumber Vibration Wavenumber Vibration

(cm-1) type (cm-1) type (cm-1) type
457 Si-O-Si 786 C-H 457 Si-O-Si
793 Si-O-Si 1231 C-O 785 C-H
966 Si-OH 1712 C=O 966 C=C
1090 Si-OR 2956 C-H 1048 CO-O
1629 C=O 3607 OH 1629 C=C
3328 OH 1712 C=O
3330 OH
Figure 6.2 (a) represent the FTIR spectra of bare silica gel, solid Ibrufen and
solid Ibrufen loaded silica gels within the range of 4000-400 cm-1. In figure 6.2
(a), the peaks at 457 and 793 cm-1 are found for the Si–O–Si bending vibration,
the peak at 1,090 cm-1 is for the Si–OR stretching vibration in silica gel. Two
peaks at 1712 cm-1 and 1511 cm-1 present in the FTIR data of Ibrufen is also
present in the FTIR data of loaded silica gel. These two peaks are absent in the
FTIR data of solid Ibrufen also. This indicates the presence of Ibrufen in silica
gel.
71
6.3.2 Solid Ibrufen entrapped in Silica gel of TEOS: ETOH: DI WATER
(1:2:2) ratio:
Figure 6.2(b): FTIR of Solid Ibrufen entrapped with silica gel matrix of TEOS: ETOH: DI
72
Bare Solid Silica gel
1:2:2 Ibrufen

457 Si-O-Si 775 C-H 457 Si-O-Si
793 Si-O-Si 1225 C-O 793 C-H
966 Si-OH 1720 C=O 959 C=C
1090 Si-OR 2956 C-H 1086 CO-O
1629 C=O 1629 C=C
3328 OH 1725 C=O
3330 OH
Figure 6.2 (b) represent the FTIR spectra of bare silica gel, solid Ibrufen and
(b), the peaks at 457 and 793 cm-1 are found for the Si–O–Si bending vibration,
the peak at 1,090 cm-1 is for the Si–OR stretching vibration in silica gel. Peak at
1725 cm-1 present in the FTIR data of Ibrufen is also present in the FTIR data of
loaded silica gel at 1720 cm-1. This peak is absent in the FTIR data of solid
Ibrufen also. This indicates the presence of Ibrufen in silica gel.
73
6.3.3 Liquid Ibrufen entrapped in Silica gel of TEOS: ETOH: DI WATER
(1:2:1) ratios:
Figure 6.2(c): FTIR of Liquid Ibrufen entrapped with silica gel matrix of TEOS: ETOH: DI
74
Bare Liquid Silica gel
1:2:1 Ibrufen

457 Si-O-Si 802 C-H 457 Si-O-Si
793 Si-O-Si 1157 C-O 802 C-H
966 Si-OH 1657 C=O 966 C=C
1090 Si-OR 3553 OH 1090 CO-O
1629 C=O 1629 C=O
3328 OH 3354 OH
3330 OH
Figure 6.2 (c) represent the FTIR spectra of bare silica gel, solid Ibrufen and
(c), the peaks at 457 and 793 cm-1 are found for the Si–O–Si bending vibration,
peaks at 798 cm-1 and 1638 cm-1 present in the FTIR data of Ibrufen is also
present in the FTIR data of loaded silica gel at 802 cm-1 and 1657 cm-1 .These
two peaks are absent in the FTIR data of solid Ibrufen also. This indicates the
presence of Ibrufen in silica gel.
75
6.3.4 Liquid Ibrufen entrapped in Silica gel of TEOS: ETOH: DI WATER
(1:2:2) ratio:
Figure 6.2(d): FTIR of Liquid Ibrufen entrapped with silica gel matrix of TEOS: ETOH: DI
76
Bare Liquid Silica gel
1:2:2 Ibrufen

457 Si-O-Si 802 C-H 456 Si-O-Si
793 Si-O-Si 1166 C-O 796 C-H
966 Si-OH 1712 C=O 962 C=C
1090 Si-OR 3559 OH 1090 CO-O
1629 C=O 1712 C=O
3328 OH 3324 OH
Figure 6.2 (d) represent the FTIR spectra of bare silica gel, solid Ibrufen and
(d), the peaks at 457 and 793 cm-1 are found for the Si–O–Si bending vibration,
Peaks at 796 cm-1 and 1712 cm-1 are present in the FTIR data of Ibrufen are also
present in the FTIR data of loaded silica gel. These two peaks are absent in the
FTIR data of solid Ibrufen also. This indicates the presence of Ibrufen in silica
gel.
77
6.4 UV-Vis spectroscopy analysis:
6.4.1 Study of release of Silica gel entrapped Insulin in SBF using UV-Vis:
Figure 6.3(a) & 6.3(b) represents the standard curve of liquid Ibrufen and solid Ibrufen
respectively. The R2 value of liquid Ibrufen is 0.99 and solid Ibrufen is 0.99.
Figure 6.3(a): Standard Curve of Liquid Ibrufen
78
Figure 6.3(b): Standard Curve of Solid Ibrufen.
6.5 Kinetic study of drug release:

The results obtained from in vitro release studies were plotted in different models according
to zero-order (cumulative amount of drug release versus time), first-order (log cumulative
percentage of drug remaining versus time), Higuchi (cumulative percentage of release versus
square root of time), and Korsmeyer–Peppas (log cumulative percentage of drug released
versus log time) equation models. The best fitted model is identified from regression
coefficient.
An in vitro dissolution study was carried out in SBF whose pH 7.0. The
absorption of a drug through the biological membrane depends on the amount of drug
available at the absorption site. This intern is dependent on the route of drug release from the
79
delivery device. The mechanism of drug release can be approximated by fitting the
dissolution data in different kinetic models. The dissolution data of all formulations were
fitted to zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. The model that best
fitted with the release data was evaluated on the basis of the regression coefficient (R2); the R2
values obtained for all formulations in various models are given below. The release profile in
burst release during the initial period (1min to 360min) and sustain release during the period
of (1hr to 168 hrs.).
6.6 Kinetics values obtained from different plots of the samples for burst
release from 1min to 360min in two different ratios:
6.6.1 Burst release of liquid Ibrufen entrapped in Silica of TEOS: ETOH:
DI WATER in (1:2:1) ratio:
Figure 6.4(a)
80
Figure 6.4(b)
Figure 6.4(c)
81
Figure 6.4(d)
Figure 6.4: (a) Zero-order release model (b) First-order release model (c) Higuchi release
Model (d) Korsmeyer-Peppas release model.
Model Zero order First order Higuchi Korsmeyer- Best fitted

Peppas for burst
release
R2 value 0.97316 0.96993 0.94419 0.89867 Zero order

n=1.54
Comparing the four different types of release model i.e., Zero-order model, first-order model,
Higuchi model & Korsmeyer-Peppas model, here we find out different R2 value of different
model of graph and it is observe that, entrapped Ibrufen in silica gel is best suitable for burst
release is Zero order.
82
6.6.2 Burst release of liquid Ibrufen entrapped in Silica of TEOS: ETOH:
DI WATER in (1:2:2) ratio:
Figure 6.5(a)
Figure 6.5(b)
83
Figure 6.5(d)
Figure 6.5(d)
84
Model Zero order First Higuchi Korsmeyer- Best fitted

model Peppas for burst
release
n=1.38
Higuchi model & Korsmeyer-Peppas model, here we find out different R2 value from
different model of graph and it is observe that, entrapped Ibrufen in silica gel is best suitable
for burst release is zero order.
6.6.3 Burst release of Solid Ibrufen entrapped in Silica of TEOS: ETOH: DI

WATER in (1:2:1) ratio:
Figure 6.6(a)
85
Figure 6.6(b)
Figure 6.6(c)
86
Figure 6.6(d)

Peppas for burst
release
2
R value 0.979 0.959 0.9631 0.96811 Zero order
1.99
different model of graph and it is that, entrapped Ibrufen in silica gel is best suitable for burst
release is Zero order.
87
6.6.4 Burst release of Solid Ibrufen entrapped in Silica of TEOS: ETOH: DI
Figure 6.7(a)
Figure 6.7(b)
88
Figure 6.7(c)
Figure 6.7(d)
89

Peppas for burst
release
n=1.34
6.7 Kinetics values obtained from different plots of the samples for
sustained release from 1hr. to 168 hr. in two different ratios:
6.7.1 Sustained release of Liquid Ibrufen entrapped in Silica of TEOS: ETOH: DI
Figure 6.8(a)
90
Figure 6.8(b)
Figure 6.8(c)
91
Figure 6.8(d)

Peppas for sustain
release
n= 1.78
92
6.7.2 Sustained release of Liquid Ibrufen entrapped in Silica of TEOS:
ETOH: DI WATER in (1:2:2) ratio:
Figure 6.9(a)
Figure 6.9(b)
93
Figure 6.9(c)
Figure 6.9(d)
94

Peppas for sustain
release

n=1.68
for burst release is Zero order.
6.7.3 Sustained release of Solid Ibrufen entrapped in Silica of TEOS:

Figure 6.10(a)
95
Figure 6.10(b)
Figure 6.10(c)
96
Figure 6.10(d)

Peppas for sustain
release
n=1.99
97
6.7.4 Sustained release of Solid Ibrufen entrapped in Silica of TEOS:
Figure 6.11(a)
Figure 6.11(b)
98
Figure 6.11(c)
Figure 6.11(d)
99

Peppas for sustain
release
n=1.984
different model of the graph and it is observe that, entrapped Ibrufen in silica gel is best
suitable for burst release is zero order.
100
CHAPTER 7
Conclusion
101
CONCLUSION
1. Silica gel is synthesized by using TEOS: ETOH: DI WATER by sol gel process. It is
then successfully loaded with solid and liquid Ibrufen. The entrapment of drug in silica
gel is confirmed by FTIR.
2. Silica gel is synthesized in two different ratios of TEOS: ETOH: DI WATER is 1:2:1
and 1:2:2. The Silica gel containing more water is found to be more porous and release
rate of Ibrufen in SBF is higher for the porous gel.
3. XRD pattern and FESEM microphotographs shows the fine size of the silica gel.
4. Release of Ibrufen from silica gel to SBF is studied.
5. Kinetics study of burst and sustained release of solid and liquid Ibrufen in SBF is
carried out. It is found to follow the zero order mechanism for both types of gel for
both solid and liquid Ibrufen.
102

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STUDY OF RELEASE KINETICS OF IBRUFEN, ENTRAPPED

IN NANOPOROUS SILICA GEL AS POTENTIAL DRUG

Under the guidance of

This is to certify that the thesis entitled “STUDY OF RELEASE KINETICS

DR. MAHUA GHOSH CHAUDHURI DR. KALYAN KUMAR CHATTOPADHYAY

This foregoing thesis is hereby approved as a credible study of an

Committee of final examination for evaluation of Thesis

NAME: MD MODASSIR ANWER

The satisfaction and euphoria that accompany the successful completion of

2.1 Preparation of Silica gel by sol gel process 24

4.3 Characterization of Silica gel using XRD, FTIR, FESEM 46

5.1 X-Ray Powder Diffraction analysis 49

6.1 Characterization of Silica gel using XRD 66

1.1. Schematic diagram of nanomaterial synthesis --------------------------------------------- 5

1. Advantages and Disadvantages of Drug Administration Routes ----------------------- 13

kinetics model for both burst and sustain release.

The properties of nanodimensional materials change significantly because of increased

1.1.2 Quantum effect:

1.3 Synthesis procedures of nanomaterials:

The synthesis procedure of nanomaterials can be broadly categorized in two techniques:

1.3.2 Bottom-up approach: Bottom up approach refers to the build-up of a material

Figure 1.1: schematic diagram of nanomaterial synthesis.

1.4.1 Sols, Gels, and Aerogels are Colloids:

1.4.3 The Sol-Gel Transition:

1.4.4 Factors that Affect Sol-Gel Chemistry:

Figure 1.2: Combination of nano-biotechnologies for the development of nano-medicine.

1.6 Drug and drug carrier:

1.7 Drug administration routes:

Drug delivery is the method or process of administering a pharmaceutical compound to

Table 1: Advantages and Disadvantages of Drug Administration Routes in general discussed:

Pain free administration Slow and unpredictable

Drug stability is good due to Taste needs to be masked

Useful if oral administration Leads to discomfort

Veins are insensitive to Patient compliance is poor

Patient compliance is high

Drug formulation and delivery administers a drug at a therapeutic concentration to a particular

Figure 1.3: structural formula of Ibrufen ( C13H18O2 ).

1.8.1 Medical uses:

1.8.2 Mechanism of action:

1. Clarkson, AJ Buckingham, DA Rogers, AJ Blackman, AG Clark, "Nanostructured

Si (OC2H5)4 + H2O HYDROLYSIS Si (OC2H5)3OH + C2H5OH

≡ Si − O −H + H− O − Si ≡ WATER CONDENSATION ≡ Si − O − Si ≡ + H2O

≡ Si − OC2H5 + H− O − Si ≡ ALCOHOL CONDENSATION ≡ Si − O − Si ≡ + C2H5OH

2.1.1 Effect of parameter:

2.2 Silica gel as drug carrier:

2.3 Drug release:

2.3.1 Burst release:

2.3.2 Sustained release:

1. Reduced potential for dose adjustment.

2.4 CHARACTERISTICS THAT MAKES DRUGS SUITABLE FOR

Protein Binding: To achieve pharmacological response unbound drug concentration is

2.6 Release kinetics:

2.6.1 Zero-order model:

Rearrangement of equation (2.5) yields:

2.6.2 First order:

Where K is first order rate constant expressed in units of time-1.

2.6.3 Higuchi model:

2.6.4 Korsmeyer-Peppas model:

Release exponent (n) Drug transport Rate as a function of

n=0.5 Fickian diffusion t-.5

1. “Current Project. “King‟s College London. http://www.kcl.ac.uk.

The major Objective of this project are given as under -