Chitosan Loaded Mucoadhesive Microspheres of Gliclazide - Journal

A B S T R A C T
RGUHS Journal of Pharmaceutical Sciences
Chitosan Loaded Mucoadhesive Microspheres of Gliclazide: In vitro and In vivo
Evaluation
Senthil A*, Thakkar Hardik R, Ravikumar and Narayanaswamy V.B
Department of pharmaceutics, Karavali College of Pharmacy, Mangalore, Karnataka.
The objective of the present investigation was to design chitosan loaded mucoadhesive microspheres of gliclazide: in vitro and in vivo
evaluation. Type 2 diabetes mellitus is a heterogeneous disease of polygenic origin and involves both defective insulin secretion and
peripheral insulin resistance. Despite the availability of new agents for treatment of type 2 diabetes mellitus, oral sulfonylureas remain a
cornerstone of therapy, because they are relatively inexpensive and are well tolerated. Since, the site of absorption of gliclazide is from
stomach thus dosage forms that are retained in stomach by mucoadhesion; would increase absorption, improve drug efficiency and
decrease dose requirements. Microspheres were prepared by simple emulsification phase separation technique. On the basis of the
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preliminary trials 3 full factorial designs were employed, to study the effect of independent variable X polymer-to-drug and the stirring
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speed X on dependent variables percentage mucoadhesion, drug entrapment efficiency and particle size. The optimized formulation
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exhibited a high drug entrapment efficiency of 60%, swelling index 0.42, Percentage of mucoadhesive after 1 hour 62% and the drug
release was also sustained for more than 10 hours. In vivo testing of the mucoadhesive microspheres to albino Wistar rats demonstrated
significant hypoglycemic effect of gliclazide.
Keywords: Mucoadhesive, Gliclazide, Chitosan, Glutaraldehyde.
INTRODUCTION
A primary object of using mucoadhesive formulations orally
would be to achieve a substantial increase in length of stay of
the drug in the GI tract. Stability problem in the intestinal
fluid can be overcome. Therapeutic effect of drugs insoluble
in the intestinal fluids can be improved. Recently, dosage
forms that can precisely control the release rates and target
drugs to a specific body site have made an enormous impact in
the formulation and development of novel drug delivery
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systems . Microspheres form an important part of such novel
drug delivery systems. They have carried applications and are
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prepared using assorted polymers . However, the success of
these microspheres is limited owing to their short residence
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time at the site of absorption . It would therefore be
advantageous to have means for providing an intimate contact
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of the drug delivery system with the absorbing membranes .
Bioadhesive microspheres have advantages such as efficient
absorption and enhanced bioavailability of drugs owing to a
high surface-to-volume ratio a much more intimate contact
with the mucus layer and specific targeting of drugs to the
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absorption site . Gliclazide, a second generation
sulphonylurea derivative and is preferred in therapy because
of its selective inhibitory activity towards pancreatic K+ ATP
RGUHS Journal of Pharmaceutical Sciences
Received: 15/7/2011, Modified: 1/8/2011, Accepted: 12/8/2011
163
Original Research Article
channels, antioxidant property, low incidence of producing
severe hypoglycemia and other haemobiological effects. The
daily dose, which is given in two fractions, is generally between
40 and 80 mg at the beginning of treatment, but the dose can
be increased also at severe conditions. Gliclazide is well
absorbed from GIT, approximately 80% is absorbed. One
dose of gliclazide has a half-life less than 10 hours with the
peak absorbance occurring at about 4-6 hours. Like most
sulphonylureas, gliclazide binds primarily to plasma albumin
(85-99%), allowing it to be distributed uniformly throughout
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the body . Thus, an attempt was made in this investigation
to use chitosan as a natural mucoadhesive polymer and
prepare microspheres. The microspheres were characterized
by in vitro and in vivo tests, and factorial design was used to
optimize the variables.
MATERIALS AND METHOD
Gliclazide was obtained as gift sample from Aurobindo
pharmaceuticals, Hyderabad, India. Chitosan (Purified,
Viscosity grade 50) was obtained from Fourt's India Limited,
Chennai. Dioctyl sodium sulfosuccinate, Heavy and Light
liquid paraffin, Glutaraldehyde and Petroleum ether (80:20)
was procured from Will son Lab, Mumbai.
Preparation of Microspheres
Microspheres were prepared by simple emulsification phase
separation technique. The different volume of cross-linking
agent glutaraldehyde was used as per method described in
RJPS, Jul - Sep, 2011/ Vol 1/ Issue 2