Artificial Cells, Blood Substitutes, and Biotechnology, 39: 330–334

Copyright © 2011 Informa Healthcare USA, Inc.

ISSN: 1073-1199 print / 1532-4184 online
DOI: 10.3109/10731199.2011.573482

Development and Characterization of Rifampicin Loaded Floating Microspheres

Pankaj Goyal and S. Gill

Nanomedicine Research Centre, Department of Pharmaceutics, Indo-Soviet Friendship College of Pharmacy, Moga (Punjab), India
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U. D. Gupta
National Jalma Institute for Leprosy and Other Mycobacterial Diseases,Taj Ganj, Agra, India

Goutam Rath, Raj K. Narang and Amit K. Goyal

Nanomedicine Research Centre, Department of Pharmaceutics, Indo-Soviet Friendship College of Pharmacy, Moga (Punjab), India

Abstract: Gastroretentive floating microspheres have a potential for enhancing the bioavailability and controlled delivery of drugs.
The present study involves development of rifampicin floating microspheres in order to increase the gastric retention time. The
microspheres were prepared by solvent evaporation technique and characterized for particle size, shape, zeta-potential, entrapment,
and release kinetics. The developed systems were almost spherical in shape. The entrapment efficiency was found to be 86.34%. The
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percentage buoyancy after 8 hours was found to be 61.06. The prepared microspheres exhibited prolonged drug release in gastric
medium and hence could be utilized for sustained delivery of anti-tubercular drugs.

Keywords: gastroretentive dosage forms, microspheres, rifampicin, tuberculosis, floating delivery systems

INTRODUCTION the CR system in the stomach for a longer time in a

The oral route is the most common and preferable route
for the delivery of drugs. This may be due to ease of
administration, patient compliance, and flexibility in
formulation [1]. However, it has limitations because of
the broad diversity in biochemical and physiological
atmospheres of the gastrointestinal tract. Thus, it can’t
be possible to get the same absorption pattern of orally
administered drugs at different parts of the gastrointesti-
nal tract (GIT). Moreover, first-pass metabolism of drugs
in the intestinal wall and liver has also been a limiting
factor for exploring the potential of oral dosage forms.
These problems can be overcome by using oral controlled
release (CR) formulations that provide controlled release
of the drugs in GIT, maintain a constant drug concentra-
tion in the serum for longer periods of time, provide better
bioavailibility, therapeutic efficacy, and possible reduc-
tion of the dose size. Moreover, oral control release sys-
tems can also be utilized to improve the gastric retention
time (GRT). Prolonged gastric retention helps to retain
predictable manner [2]. The gastro-intestinal residence
time determines the time period available for drug release
from oral controlled release delivery systems within
the GIT [3]. Several approaches have been utilized to
increase the gastric retention time, i.e. floating systems,
mucoadhesive dosage forms, high-density systems, super-
porous hydrogel, swelling and expanding systems, and
magnetic systems. These systems have more flexibility in
dosage design than conventional dosage forms [4–6].
Gastroretentive formulations are a device that remains
buoyant in gastric juice for a longer time and releases
drugs in a predetermined and predictable manner. Float-
ing Drug Delivery Systems (FDDS) can be designed in
both single and multiple unit systems. Generally, single
unit floating devices are not suitable for control release
formulation because of variability release patterns and
bioavailability in GIT [7,8]. However, multiple unit par-
ticulate dosage forms (e.g. microspheres) have shown bet-
ter applicability due to increased surface area of dosage
forms that will provide uniform distribution of drugs in

Address correspondence to: Dr. Amit K. Goyal, Nanomedicine Research Centre, Department of Pharmaceutics, I. S. F. College of
Pharmacy, G. T. Road, Moga 142001 (Punjab), India. E-mail: amitkumargoyal1979@yahoo.com
330
 Rifampicin Loaded Floating Microspheres
Table 1. Micromeritics properties of developed rifampicin
microspheres.
Micromeritics properties Rifampicin microspheres
Angle of repose 41.05°  5
Bulk density (g/cm3) 0.133
Tapped density (g/cm3) 0.183
Carr’s Index (%) 27.32
Hausner’s ratio 1.25
% Compressibility Index 27.27
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GIT and provide a desired release pattern, which reduces
variability in absorption and other associated problems
[8–11]. These microspheres are characteristically free
flowing powders having a size less than 200 μm and
remain buoyant in gastric content for a prolonged period.
As the system floats in gastric fluids, the drug releases
slowly at the desired rate, resulting in enhanced gastric
absorption with reduced fluctuations in plasma drug
concentration [8,12]. Kawashima et al. [13] prepared the
hollow microspheres of ibuprofen by the emulsion solvent
diffusion method. Soppimath et al. [14] prepared the float-
ing microspheres using natural polymers such as chitosan,
xanthan gum, gelatin, and pectin. Muthuswamy et al. [15]
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also prepared the floating microspheres of lanzoprazole
and cimetidine using semi-synthetic polymers such as methyl
cellulose and hydroxyl methyl cellulose. Dennis et al. [16]
Figure 1. Photomicrograph of developed formulation at magnification 250 X.
331
proposed a loose powder-filled floating capsule that will
float on gastric juices and thus improve the drug availability.
Muller et al. [17] patented a floating drug delivery system
that has lower density than gastric juice, due to incorporation
of at least one porous structural element, such as foam or
a hollow body.
The objective of the present investigation was
to prepare a floating microsphere of rifampicin in order
to achieve an extended release in the upper GIT, which
may result in an enhanced absorption and thereby
improved bioavailability. Rifampicin is a first-line anti-
tubercular agent that is used with other anti-tubercular
agents to treat tuberculosis caused by mycobacterium
tuberculosis. It is mainly absorbed through the stomach
and is better absorbed in the acidic environment of the
stomach. But in combination with isoniazid, rifampicin
forms 3-formyl rifampicin, thereby reducing the bioavail-
ability of rifampicin from oral route [18]. Gastro-reten-
tive systems can remain in the gastric region for several
hours and hence significantly improve the gastric resi-
dence time of drugs. Prolonged gastric retention further
improves the bioavailability of rifampicin and reduces
drug waste by minimizing the interaction of rifampicin
with isoniazid.
In the present study, rifampicin loaded floating
microspheres were prepared by the solvent evaporation
 332
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Figure 2. Particle size analysis of developed formulation.
method and characterized for their size, shape, percent
yields, flow properties, and in-vitro buoyancy and in-vitro
release.
MATERIALS AND METHODS
Rifampicin was received as a gift sample from Lupin
Pharmaceutical (India) Ltd., Mumbai. Hydroxy propyl
methyl cellulose (HPMC) and ethyl cellulose (EC) were
purchased from Himedia Pvt. Ltd., India. All the other
ingredients used were of analytical grade.
PREPARATION OF FLOATING
MICROSPHERES
Rifampicin loaded floating microspheres were prepared
by using the solvent evaporation method as employed
by Srivastava et al. [8]. EC, HPMC, and Rif were dis-
solved in a mixture of ethanol and dichloromethane
having the ratio of 1:1. This solution was poured slowly
into the water containing 0.01% Tween 80 and stirred for
40 minutes to allow the volatile solvent to evaporate. The
microspheres were filtered, washed with water, and dried
in vacuum.
P. Goyal et al.
Figure 3. Zeta-potential analysis of developed formulation.
CHARACTERIZATION OF MICROSPHERES
Size and Shape of Microspheres
The size of microspheres was determined using a
microscope fitted with an ocular micrometer and stage
micrometer (Motic Microscope, India). Mean particle size
and zeta potential of prepared systems were determined
by a photon correlation spectroscopy using a Delsa Nano
(Beckman Coulter, UK).
Determination of Percent Yield. Thoroughly dried
microspheres were collected and weighed accurately. The
percentage yield was then calculated.
weight of microspheres
% yields   100
weight of polymers
In-vitro Buoyancy Percentage. Floating microspheres
(50 mg) were placed in 0.1 N HCI (100 ml) and stirred
at 100 rpm. The floating microspheres were separated by
filtration. The microspheres were dried in a desiccator
overnight [19]. The % buoyancy was calculated using the
formula below.
 Rifampicin Loaded Floating Microspheres
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Figure 4. Photograph showing the floatability of developed formulation at different time intervals: (A) 1 hrs; (B) 2 hrs; (C) 3 hrs;
(D) 4 hrs; (E) 5 hrs; (F) 6 hrs; (G) 7 hrs; (H) 8 hrs.
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weight of floating microspheres
% buoyancy   100
weight of floating microspheres
 weight of settled microspheres
ENTRAPMENT EFFICIENCY
To determine the entrapment efficiency, 50 mg micro-
spheres were taken, thoroughly triturated, and suspended
in a minimal amount of alcohol. The suspension was
suitably diluted with water and filtered. Drug content
was analyzed spectrophotometrically at 475 nm.
IN-VITRO RELEASE
The drug release of rifampicin loaded microspheres was
determined using a USP XXIV basket-type dissolu-
tion apparatus [20]. A weighed amount of microspheres
Figure 5. In-vitro drug release profile of rifampicin loaded floating
microspheres.
333
equivalent to 50 mg drug was placed in the basket. Simu-
lated gastric fluid was used as the dissolution medium and
maintained at 37°C at 100 rpm. 5 ml sample was with-
drawn after a 30 min interval for 1 hour and was passed
through a membrane filter. Other samples were withdrawn
hourly for 8 hours. The samples were then analyzed spec-
trophotometrically at 475 nm to determine the concentra-
tion of drug present in the dissolution medium. The initial
volume of the dissolution fluid was maintained by adding
5 ml of fresh dissolution fluid after each withdrawal.
RESULTS AND DISCUSSION
Floating microspheres were prepared by solvent diffusion
to create the hollow inner core. Polymers were dissolved
in an organic solvent and then emulsified with an aqueous
drug solution containing surfactant to form oil in water
emulsion. After the formation of a stable emulsion, the
organic solvent was evaporated by continuous stirring. The
solvent removal lead to polymer precipitation at the o/w
interface of droplets, forming a cavity, and thus imparted
the floating properties in the developed microspheres.
In the present study, floating microspheres were
prepared by the solvent evaporation technique using
HPMC and EC in the 1:6 ratio. The photomicroscopic
images confirm that floating microspheres were almost
spherical in shape with no visible major surface irregular-
ity (Figure 1). The particle sizes of prepared formulation
were found to be 17.5  4.45 μm; however, zeta potential
of developed formulation was found to be 2.5  0.1 mV
 334
(Figures 2 and 3). The percentage yield of the developed
formulation was calculated and found to be 78.57%. The
high entrapment efficiency of rifampicin is believed to be
due to its poor aqueous solubility. The drug entrapment
was found to be 86.34%  2.34.
In-vitro buoyancy was carried out to investigate the
floatability of the prepared floating microspheres. The
floating behavior of the rifampicin microspheres was car-
ried out in simulated gastric fluid. The lag time of floating
microspheres was found to be zero. The HPMC and EC
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in the ratio of 1:6 showed the excellent buoyancy time
with no lag time. The formulation was buoyant for more
than 8 hours. A photomicrograph of the developed formula-
tion has also confirmed the floatability properties of the mi-
crospheres (Figure 4). 61.6 % of the formulation remained
buoyant after 8 hours, indicating that the bulk density of
the formulations remained unchanged. This could be due to
poor wettability of ethyl cellulose. Floating microspheres
showed sustained release of the drug in an acidic environ-
ment and the drug release was found to be approximately
linear. The percentage of rifampicin released from the
formulated products is shown in Figure 5. One of the
objectives of the present study was to control the release
For personal use only.
of the rifampicin in the acidic medium to minimize the
concentration-dependent degradation of rifampicin when
administered along with isoniazid. Approximately 18% of
the drug was released initially within half an hour. The total
drug release from the microspheres after 8 hour in the simu-
lated gastric fluid was 79.45% (Fig. 5). The study demon-
strated that floating microspheres are useful for the delivery
of sparingly soluble and insoluble drugs. The positioned
gastric release is useful for efficient absorption of drugs
through the stomach, thus enhancing their bioavailability.
CONCLUSION
For better management of tuberculosis and in order to
sustain the release of rifampicin in the stomach, an
attempt was made to prepare floating microspheres of
rifampicin using HPMC and EC. Studies demonstrated
better entrapment and sustained release patterns. More-
over, the developed system has shown good buoyant abil-
ity. It is known that, as the solubility of a drug decreases,
the time available for drug dissolution becomes less
adequate and thus the transit time becomes a significant
factor affecting drug absorption. This could be advanta-
geous to improve the bioavailability of rifampicin for the
efficient management of tuberculosis. The microspheres
could be compressed into tablets, filled into capsules, or
formulated into oral suspensions for reconstitution.
Declaration of interest: The authors report no conflicts of
interest. The authors alone are responsible for the content
and writing of the paper.
P. Goyal et al.
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