Subject: Pharm Chem -1 LEC (Chemistry & Pharmacy of Inorganic Medicinals)

Year& Section: BS PH- 3A, 3B, 3C, 3D and 3E

Compiled & Enhanced by: BENXIRGO, RPh. Revised & Updated on: Sept 2016

Unit X. Inorganic Pharmaceutical Excipients 3 Hours

1. Tableting Aids 2. Suspending Agents 3. Others

TABLETS are solid dosage forms usually prepared with the aid of suitable pharmaceutical
Excipients. They may vary in size, shape, weight, hardness, thickness, disintegration, and dissolution
characteristics and in other aspects, depending on their intended use and method of manufacture. Most
Tablets are used in Oral administration of Drugs. Many of these are prepared with colorants and coating
of various types. Other tablets, such as those administered sublingually, buccally, or vaginally are
prepared to have features most applicable to their particular route of administrations.
Tablets are prepared primarily by compression, with a limited number prepared by molding.
Compressed tablets are manufactured with tablet machines, capable of exerting great pressures in
compacting the powdered or granulated material.
I.Tableting Aids:
The compounding of a tablet is a complex operation. In addition to the active ingredients, the tablet
contains BINDERS, FILLER Material (or DILUENTS) which brings the tablets up to acceptable size,
sometimes a Disintegrating Agents, and Lubricants. The Tablet must be of such COMPACTNESS, that it
does not break during packaging and subsequent handling, but still can disintegrate when properly
located in the GIT. Furthermore, inactive ingredients in the tablet must not bind the active ingredients as
this could prevent its systemic absorption.
1. DILUENTS (or FILLERS) agents which add the necessary BULK to a formulation to
prepare tablets of the desired size. These agents are physiologically INERT. Without them, many
tablets would be too small. For convenience, since most doses of drugs are in Mg.
range. LACTOSE is a common diluent. However, inorganic agents like calcium sulfate and
colloidal silicon dioxide are also used.

Calcium Sulfate NF XV (CaSO4) Synonyms: Gypsum; Alabaster; Satin Spar; Light Spar
for the dehydrate calcium sulfate
Properties: Calcium NF XV is anhydrous or contains two molecules of water of hydration
(CaSO4.5H2O). It occurs as a fine to slightly yellow-white, odorless powder.
Uses: The anhydrous form is marketed as Drierite and used as a rechargeable laboratory and industrial
desiccant. Both the anhydrous and dehydrate forms are used extensively as table diluent. Although not
official, the hemihydrate of Calcium Sulfate (CaSO4.1/2 H2O) commonly known as Plaster of Paris, is
widely used for making supportive casts by physicians and dental impressions by dentists.

Colloidal Silicon Dioxide NF XV (SiO2)

Properties: Colloidal silicon dioxide NF is a submicroscopic fused silica prepared by the vaporphase
hydrolysis of a silicon tetrachloride (SiCl4) at 1,100C. It occurs as light, white non-gritty powder of
extremely fine particle size. It is insoluble in water and in acids.
Uses: As a tablet diluent, suspending and thickening agent, behind in the mold.

Others: KAOLIN; MANNITOL; Microcrystalline Cellulose; Calcium carbonate (ppted);

Dibasic Calcium phosphate; SORBITOL; STARCH; Powdered cellulose

2. BINDERS or ADHESIVES agents which promote adhesion of the particles of the

formulation, allowing a granulation to be prepared and maintaining the integrity of the final tablet.
Examples:. ACACIA, Alginic acid;CMC; Gelatin; Liquid Glucose; PVP/Povidone;
Methylcellulose; Ethylcellulose; Pregelatinized Starch

3. ANTIADHERENTS/GLIDANTS/LUBRICANTS/ or LUBRICATING AGENTS

enhance the flow of the materials into the tablet dies, minimized wear of the punches and dies,
prevent fill material from sticking to the punches and dies, and produce tablets with a sheen.
Examples: GLIDANTS: Colloidal Silica/ Cornstarch/ TALC
 During the compression of the granulated mixture into a tablet, heat is generated and the tablet
can be tightly held In the mold of the tableting machine making ejection very difficult, especially with
high speed tablet pressed. For this reason, Lubricants are added to the mixture making it possible to
eject the tablet cleanly, leaving no residue behind the mold. Most of the LUBRICANTS are insoluble
soaps, having metal salts of fatty acids. Official compounds include:

Examples: 1. Calcium stearate, NF XIII

2. Magnesium stearate, USP XVIII

Others: Mineral Oil; Stearic acid; Zinc stearate

4. DISINTEGRANTS or DISINTEGRATING AGENTS promote breakup of the tablets after

the administration to smaller particles for ready drug availability.
They are used in solid forms to promote Disruption of the Mass into Smaller Particles more readily
dispersed or dissolved.
Examples: Alginic acid; Polacrilin potassium (eg. Amberlite); Sodium alginate; Sodium starch
glycolate; Starch

5. MISCELLANEOUS ADJUNCTS such as COLORANTS and FLAVORANTS.

COLORANTS used to impart color to Liquid and Solid (eg. Tablet and capsules) preparations.
Examples: FD&C Red# - 3; FD&C Red #-20; FD&C Yellow #-06; FD&C Blue #-02;
D&C Green #-05; D&C Orange #-05; D&C Red #-08; CARAMEL; Ferric oxide, Red
FLAVORANTS Used to impart flavor and often odor to a preparation. In addition to the Natural
Flavorants listed, many synthetic ones are used.
Examples: Anise Oil; Cinnamon Oil; Cocoa; Menthol; Orange Oil; Peppermint Oil; Vanillin

II.SUSPENDING AGENTS:
There are a number of Pharmaceutical Aids used as Suspending Agents. Some act by altering the
surface character of the solvents (SURFACTANTS), and other are Thickening Agents. Found in the
latter category are the vegetable gums, silicates and clays. Official compounds, include:
Example: BENTONITE, USP XVIII Bentonite Magma, USP XVIII

III. Other Pharmaceutical Excipients:

1. ACIDIFYING AGENTS
2. ALKALINIZING AGENTS 25. SWEETENING AGENTS
3. ADSORBENTS 26. TABLET ANTIADHERENTS (Above)
4. AEROSOL PROPELLANT 27. TABLET BINDERS (Above)
5. AIR DISPLACEMENT 28. TABLET & CAPSULE DILUENT (Above)
6. ANTIFUNGAL PRESERVATIVES 29. TABLET COATING AGENT
7. ANTIMICROBIAL PRESERVATIVES 29.1 Sugar Coating
8. ANTIOXIDANTS 29.2 Film Coating
9. BUFFERING AGENTS 29.3 Enteric Coating
10. CHELATING AGENTS 30. TABLET DIRECT COMPRESSION
EXCIPIENT
11. COLORANTS 31. TABLET DISINTEGRANT (Above)
12. CLARIFYING AGENTS 32. TABLET GLIDANTS (Above)
13. EMULSIFYING AGENTS 33. TABLET LUBRICANTS (Above)
14. ENCAPSULATING AGENTS 34. TABLET or CAPSULE OPAQUANT
15. FLAVORANTS (ABOVE) 35. TABLET POLISHING AGENTS
16. HUMECTANTS 36. TONICITY AGENTS
17. LEVIGATING AGENTS 37. VEHICLES
18. OINTMENT BASES 37.1 Flavored, Sweetened Vehicle
19. PLASTICIZERS 37.2 Oleaginous Vehicle
20. SOLVENTS 37.3 Sterile Vehicle
21. STIFFENING AGENTS 38. VICOSITY INCREASING AGENTS
22. SUPPOSITORY
23. SURFACTANTS
24. SUSPENDING AGENTS (Above)
III. Other Pharmaceutical Excipients: ( from ACIDIFYING Agent CHELATING Agent )
III. Other Pharmaceutical Excipients: ( from COLORANT SOLVENT )
III. Other Pharmaceutical Excipients: ( from STIFFENING Agent Tablet / Capsule Agent )
III. Other Pharmaceutical Excipients: ( from Tablet Coating Agent to VEHICLE )
III. Other Pharmaceutical Excipients: ( from VEHICLE Types VISCOSITY INCREASING Agent )

XI. Radiopharmaceuticals and Contrast Media

Discussion of Chemistry have centered upon those properties and reaction of atoms and molecules
involving electrons in the outermost atomic and molecular orbitals. In direct contrast, this chapter will deal
primarily with nuclear reactions, that is, reactions that occur within nuclei of certain atoms, or between the
nucleus and the innermost electrons.

Radiopharmaceuticals: radioactive drug or substance. Use: diagnosis and treatment of

disease (Encarta,2009). These are radioactive tracers and specialized radioactive detectors,
employed/utilized in nuclear medicine procedures to follow these compounds as they distribute to various
organs or tissues.
Radioisotopes: they are radionuclides with the same number of protons and a different number of
neutrons.
In the electrically neutral atom, the number of electrons is equal to the number of protons in the
nucleus. Furthermore, the number of protons in the nucleus is equal to the atomic number of atoms,
which determines its properties. The atomic number of an atom is also characteristic of the particular
element of which the atom is a part. In fact, the atomic number is the determinant of element, in that,
all the atoms composing an element have the same number of protons and, therefore, are not exactly
alike.
Most Elements contain a certain percentage of atoms, which differ in atomic weight or mass from
the majority of atoms present. These different forms of elements are known as isotopes, and they vary
in the number of neutrons in the nuclei of their atoms. Isotopes of a particular elements, then, have
the same atomic number (same number of protons), but different MASS Numbers (Differing number of
Neutrons).
 The isotope of a particular element has the same chemical and physical properties. The only variation
that is usually found is in the kinetics or rates of chemical reactions involving the isotopes, since the mass
is a very important aspect of reaction rates.
Other general facts about Isotopes are that the natural abundance of stable form of elements is
constant regardless of the form in which the element is found. Examples are as follows:
1. Carbon = 1% of C and 99% C
2. Chlorine =75% of Cl and about 25% Cl.

Two Major Types of isotopes are found in Nature:

1. Stable Isotopes maintain their elemental integrity, and do not decompose into
other isotopic or elemental forms.
2. Unstable /Radioactive Isotope decomposed or decay, by emission of nuclear
particles into other isotopes of the same or different elements.

The decay is characteristic for a particular isotope, and continues a stable isotopic level is achieved.
Since the transition from one isotope to another, whether it is the same element or not, involves nuclear
transformations, the chemistry of radioactive isotopes differs from the chemistry of stable isotopes by the
additional aspects of the nuclear reactions.
Some unstable isotopes exist as or pass though metastable state. Metastable isotopes are
characterized by slow rate of decay allowing an accumulation of the metastable form which often gives
the appearance of the stable form of the isotope. In reality the metastable form is decaying at a rate
significantly slower than the parent isotope.
Not all radioactive isotopes are found naturally in element. In fact, a large number of unstable isotopes
are produced synthetically for their usefulness in chemical, geological and biological applications. The
production of radioactive isotopes usually invo0lves the bombardment of atomic nuclei, with subatomic
particles, i.e., neutrons or electrons, to produce unstable nuclei of the same or different elements

RADIOACTIVE DECAY PARTICLES: When a radioactive isotope decays, it does so

with the emission of certain particles or quantities of energy that is characteristics of the
particular isotopes involved. There are numerous species that have been identified as particles of
nuclear origin. However, the major decay particles of interest here include alpha particles, beta
particles, including negatrons (Electrons of nuclear origin), and Positrons, gamma rays, and x-
rays.

1. Alpha particles (, He). These radiations are by far the heaviest and slowest of all
radioactive emissions. The particle is actually a Helium nucleus, containing 2-protons and 2neutrons
for an atomic mass of 4 (wt. approx. 6.6 x10 g.) and atomic number of 2. It is the most highly
charged nuclear species, with a charged of +2, giving it a very high ionizing power, upon interaction
with air or other media. Alpha particle move at a relatively slow speed, averaging about 0.1 the speed
of light (3.0 x10 cm/s, or 186,000 mi/s), and their penetrating power is very low. They can be
stopped ny a sheet of paper or by a very thin sheet of aluminum foil. These particles will travel only- 3-
8 cm in air.
Alpha radiation is usually emitted only from elements having an atomic number greater than 82.
Isotopes emitting alpha particles will decay to the element having a mass number of 4 less and
atomic number of 2 less than the original isotope. However the emission of alpha radiation is usually
accompanied by other radiation. The emission of alpha radiation is illustrated below with radium-226
(the radium isotope having a mass number of 226) in rx.
Ra Rn + (or He)
The Low penetrating power of particle makes isotopes emitting this type of radiation rather useless
for biological application, because these particles cannot penetrate tissue.

2. Beta Particles ( or ). This is the terminology normally applied to radiation which

may be further described as an electron of nuclear origin. particles are negatively charged species
having the mass of an electron (approx. 9.1 x10 g.) Since these radiations are lighter than -
particles by a factor of 10, they move at faster velocities often approaching 0.9 the speed of light.
Their emissions from elements do not alter the atomic mass, but do alter the atomic number. The
 negative charged causes -particles to produce ionization of molecules when they pass through
various media.

Depending upon their energy, particles have more penetrating power than particle and are
often able to travel from 10-15mm in water or penetrate almost 1-inch thicknesses of aluminum.

particles, sometimes called NEGATRONS, are emitted by unstable nuclei having neutrons
in excess of protons. If the Neutron or proton ratio exceeds stable limits, a transformation of a
neutron to a proton will occur, with the expulsion of radiation. Elements undergoing this type of
transformations will decay to the element having the next highest atomic number.
n p +

An example of decay is illustrated in Reaction with carbon -14. C

N +
Elements may emit radiation alone or in combination with other types of radiation. As mentioned
above, particles may produce ionizations as they passed through various media; however, interactions
with surrounding nuclei may cause acceleration in the particle depending upon the atomic number of
charge of the nucleus. As a result of this process, some of the energy of the particle is seen as
electromagnetic radiation known BREMSTRAHLUNG or Braking radiation. This radiation is similar to
gamma radiation. Many isotopes emitting radiations have useful biological applications since the
radiations will penetrate tissues.

Another type of radiation that is not as common as the negatively charged particle discussed
above is seen in the emission of POSITRON (). This particle is identical to the electron with the
exception of having a positive charged. It is emitted from nuclei having a proton/neutron ration above
stable limits. According to reaction, a proton can be transformed into a neutron accompanied by the
emission of a positron.
p n +
Elements emitting Positron will do so only to a small fraction of their total radioactive emissions,
and will decay to the element having the next lowest atomic number. An illustration of Positron Beta
Decay is shown in rx w/zinc-65.
Zn Cu +
Positrons are of little importance in biological applications. They are very short-lived species in that
they undergo annihilation reactions with electrons to produce gamma radiation or annihilation photons.

3. Gamma Radiation (). This Ray may be best described as a Photon of Electromagnetic
Radiation. It demonstrates both wave and particle properties, as do electrons and beta Particles.
The rays are of short wavelength (10 to 10) similar to x-rays, and travel at the speed of light.
They have no mass and no charge, but they are of very high energy, giving them excellent
penetrating power. Very thick lead or concrete shielding is required to protect against the radiation
from strong gamma-emitting sources. The fact that this radiation is uncharged indicates that its
ionizing power is poor. However, gamma rays can interact with atoms and molecules in a particular
medium to produce ions and free radicals secondarily by dislodging electrons from orbitals. The high
penetrating power of these packets of energy increases the opportunity for secondary ionizations.

The Emission of Gamma rays from an element results in a lowering of the nuclear energy level of
the element, but no elemental charge is noted unless one of the other types of radiation is also
emitted. If gamma emission does occur alone, it will involve the transition of a metastable state of an
isotope either to a stable form or to a form of the same isotope which will continue to decay by other
means. For example, consider rx involving the metastable state of Cobalt-59 with the subsequent
emission of a gamma (n,) as indicated by the notation on the far left of the reaction.

Co (n,)) Co Co + Ni + + 2
4. K-Capture. A type of Radiation similar to gamma rays is seen in the emission of x-rays through a
process known as K-capture. This type of radiation is produced by isotopes with an unstable
proton/neutron ratio but with insufficient energy to emit positron.
Alternatively the nucleus captures an electron from the so called K-Shell (1s Orbital, and can occur
also from the L Shell or 2s orbital), which combines with a proton to form a neutron.

The rearrangement of the orbital electrons takes place with the release of energy in the form of x-
rays. Although the process involves the nucleus, the energy release comes largely from the
necessary electronic rearrangements.
The loss of a proton in a nucleus indicates that the isotope will decay to the element having the
next lowest atomic number. Mercury-197 is an example of an isotope emitting radiation by kcapture.
K-Capture
Hg ------------------------------ Au + X-Ray

Isotopes emitting gamma radiation are used frequently in biological applications. The penetrating
power of this form of radiation is sufficient to reach deep into tissues, and to be detected outside of the
body.

Kinteics Of Isotope Decay:

Due to spontaneous decay, the activity of the radioactive sample diminishes with time. The rate of the
isotopic decay is dependent on the concentration of the radioactive atoms present. This means that the
decay process should follow First Order Kinetics which describes the rates of reactions
proceeding in a manner independent of reactant concentrations.

Biological Effects of Radiation:

The effect of radioactive particles impinging upon biological tissue depends upon a number of factors
related to the ability of the radiation to penetrate tissue, the energy of the radiation, the particular tissue
and surfaced area exposed, and the dose rate of the radiation.
The destructive aspect of radioactivity is directly related to its interaction with molecules present in the
tissue to form abnormal amounts of ions and / or free radicals. These chemical species can alter the local
pH or serve to initiate free radical chain reactions resulting in the production of peroxides or other toxic
compounds. These and other events can create a hostile environment for tissue cells leading to necrosis
and, ultimately, complete destruction of the tissue or organ.
Water is the most abundant molecule in most tissues and is most probable reactive species in the path
of ionizing radiation, although, other biochemicals may be involved.

2. Radiopharmaceutical Preparations>>> ASSIGNMENT for the FINALSJust

WAIT for Further Instructions: