Chitosan Loaded Mucoadhesive Microspheres of Gliclazide - Journal

OBJECTIVES
1) To formulation of controlled mucoadhesive buccal drug
delivery system by using central composite design.
2) To improve the bioavailability by passing the first pass
effect.
3) To perform the evaluation studies for thickness,
hardness, weight variation, friability and In vitro drug release.
MATERIALS AND METHOD
Materials
Prakash Rao B et al./ Formulation and Evaluation of Mucoadhesive Buccal Drug Delivery System of Metoprolol Tartrate by Using Central Composite Design
Metoprolol Tartrate was obtained as a gift sample from
Novartis pharmaceutical LTD (Mumbai, India). Carbopol
934P and magnesium stearate were purchased by S.D Fine
Chem. LTD. (Mumbai, India). HPC was received as gift
sample from Strides Arco labs LTD (Bangalore, India). All
other chemicals and reagents were of analytical grade.
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Experimental Design
Central composite design (CCD) was selected for the
development of the formulation. CCD has three groups of
design points, two-level factorial or fractional factorial design
points, axial points (sometimes called "star" points) and
central points. Central points are usually repeated 4-6 times to
get a good estimate of experimental error. Central composite
designs have 5 levels of each factor: -Alpha, -1, 0, 1, and
+Alpha (Table 1). Effect of carbopol (A) and effect of HPC (B)
was selected as independent variables. Higher (+1) and lower
(-1) value of the independent variables were selected and
calculate the alpha value. These values were put in the
optimization software and get the different formulation given
in the (Table 2). The drug release after 8 hours (R 1),
bioadhesive strength (R 2), T 50% (time for 50% of drug release)
(R3) and diffusion coefficient (n) (R4) were selected as
responses.
Preparation of Buccal Tablet
Buccal tablets of MT were prepared by direct compression
method. All the ingredients without magnesium stearate were
accurately weighed and mixed in mortar with a pestle for 10
minutes to get the uniform powder. After sufficient mixing of
drug and polymer, magnesium stearate was added and mixed
for 3 min. The blended powder was compressed into tablets by
using the Rimek mini press –I compression machine. The
quantities of various ingredients are shown in (Table 2).
Evaluation of Buccal Tablets
Thickness
Thickness of the tablet was measured by using the digital
vernier callipers (Aerospace, china).Thickness is expressed in
15
millimeters.
Hardness
The hardness of the tablet was measured using the Monsanto
hardness tester (Scientific engineering corp., Delhi, India). It
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is expressed in Kg/cm .
Weight Variation Test
20 Tablets were taken from each batch and individually
weighed by Electronic balance. Average weight of the tablets
was calculated and deviation from the actual weight was
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determined.
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Friability
Friability generally refers to the loss in weight of tablets in the
containers due to the removal of fines from the tablet surface.
Friability generally reflects poor cohesion of tablet
ingredients. 10 tablets were weighed, initial weight of these
tablets were recorded and placed in Roche friabilator and
rotated at the speed of 25 rpm for 100 revolutions. Then,
tablets were removed from friabilator, dusted off the fines and
Table 2: List of working formulations
Run Carbopol( X 1 ) HPC ( X 2 ) Design
(mg) (mg) point
F-1 65.00 65.00 Centre
F-2 65.00 65.00 Center
F-3 15.50 65.00 Axial
F-4 65.00 65.00 Centre
F-5 30.00 30.00 Fact
F-6 30.00 100.00 Fact
F-7 100.00 30.00 Fact
F-8 100.00 100.00 Fact
F-9 65.00 65.00 Centre
F-10 114.50 65.00 Axial
F-11 65.00 15.50 Axial
F-12 65.00 114.50 Axial
F-13 65.00 65.00 Centre
Each formulation contain 50 mg of MT
Table 1: Factors and their corresponding levels implemented for the construction of CCD
Independent
variable(Factor)
-Alpha( α)
-1 0 +1 +alpha(α)
Carbopol 15.50 30 65 100 114.50
HPC 15.50 30 65 100 114.50
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RJPS, Jul - Sep, 2011/ Vol 1/ Issue 2