98 6. FORMULATIONS, EVALUATION AND IN-VIVO STUDY OF MUCOADHESIVE DRUG DELIVERY SYSTEM USING A 2 3 FULL FACTORIAL DESIGN Numerous buccal mucoadhesive drug delivery systems have been developed to prolong the drug release. The biopharmaceutical classification system (BCS) 153,154 is used to group the API depending upon the solubility and permeability characteristics of the drug. BCS Class II compounds are poorly water soluble and highly permeable. Nifedipine was chosen as a model drug to formulate and optimize the sustained release mucoadhesive drug delivery system using 2 3 factorial designs. Nifedipine belongs to BCS Class II compound for treatment of angina pectoris. BCS Class III compounds are highly soluble and poorly permeable. Hydralazine HCl was chosen as a model drug to formulate and optimize the Sustained release mucoadhesive drug delivery system using 2 3 factorial designs. Hydralazine HCl belongs to BCS Class III compound for treatment of hypertension and congestive heart failure. 6.1 Formulation of nifedipine and Hydralazine HCl mucoadhesive buccal drug delivery system using a factorial design by two level-three factor A factorial design was applied in this experiment where the effects of different conditions or factors, on experimental results are to be elucidated. A factor is an assigned variable such as concentration, temperature, lubricating agent, drug treatment or diet. The choice of factors to be
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6. FORMULATIONS, EVALUATION AND IN-VIVO STUDY OF MUCOADHESIVE DRUG DELIVERY SYSTEM USING A 23 FULL
FACTORIAL DESIGN
Numerous buccal mucoadhesive drug delivery systems have been
developed to prolong the drug release. The biopharmaceutical classification
system (BCS) 153,154 is used to group the API depending upon the solubility
and permeability characteristics of the drug.
BCS Class II compounds are poorly water soluble and highly
permeable. Nifedipine was chosen as a model drug to formulate and
optimize the sustained release mucoadhesive drug delivery system using 23
factorial designs. Nifedipine belongs to BCS Class II compound for treatment
of angina pectoris.
BCS Class III compounds are highly soluble and poorly permeable.
Hydralazine HCl was chosen as a model drug to formulate and optimize the
Sustained release mucoadhesive drug delivery system using 23 factorial
designs. Hydralazine HCl belongs to BCS Class III compound for treatment
of hypertension and congestive heart failure.
6.1 Formulation of nifedipine and Hydralazine HCl mucoadhesive buccal drug delivery system using a factorial design by two level-three factor
A factorial design was applied in this experiment where the effects of
different conditions or factors, on experimental results are to be elucidated.
A factor is an assigned variable such as concentration, temperature,
lubricating agent, drug treatment or diet. The choice of factors to be
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included in an experiment depends on experimental objectives and is
predetermined by the experimenter.
In this present investigational research work the mucoadhesive buccal
tablets of nifedipine and hydralazine HCl was prepared separately employing
23 randomized full factorial design by using xanthan gum or Pectin,
carbopol-974P, HPMC-K4M, In this experimental model, our target is to
determine how the t90% of drug release and mucoadhesive characters can be
affected by adjusting three parameters, concentration of polymers xanthan
gum or Pectin, HPMC-K4M, carbopol-974P, of the mucoadhesive buccal
tablets. For each of these factors, the levels will explain for use in this 2-
level experiment.
23 full factorial studies were designed to determine the interaction of
three independent variables at two levels (low and high level concentration).
The factorial design, simplifying the method and highlighting the
relationships between variables, it also allows the effects of manipulating a
single variable to be isolated and analyzed singly.
6.1.1 Experimental design (23 full factorial)
A 23 full factorial design was created to determine and optimize the
effect of the three formulation factors using t90% as response factor.
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Table.6.1 23factorial design represents three variables at two levels
Level Factor A Factor B Factor C High + + + Low - - -
Table.6.2 Concentration of polymers variables
Level Factor A Factor B Factor C
High 60 40 40
Low 35 25 20
Table.6.3 23 factorial design represents three variables Factors
Std Factor A Factor B Factor C
A -1 -1 -1 A +1 -1 -1 B -1 +1 -1
AB +1 +1 -1 C -1 -1 +1
AC +1 -1 +1 BC -1 +1 +1
ABC +1 +1 +1
+1 denotes High Level, -1 denotes Low Level
Factor A, B, C are Variables
6.1.2 Statistical optimization technique
In this present research work nifedipine and hydralazine HCl
mucoadhesive buccal tablets optimized has been done by statistically using
23 full factorial designs. In this study, three variables factors were evaluated
each at two levels, and investigational were performed at all eight possible
combinations. In which three variables namely such as xanthan gum or
pectin, HPMC-K4M, carbopol-974P, was kept at two levels, one is low level
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and another one is high level. Except the optimization phase whose purpose
was validated by extra design check point and main interactive influences
were tested using statistical method. The eight formulation of optimization
phase were categorized in to four groups for ease of investigation and
similarity as follows.
Group 1: All Three changeable factors at Low Level
Group 2: Any one of the changeable factors at High Level
Group 3: Any two of the changeable factors at high level
Group 4: All three changeable factors at high level
6.1.3 Formulation of mucoadhesive sustained release buccal tablets
containing nifedipine
Mucoadhesive sustained release buccal tablets155 of nifedipine were
prepared by a direct compression technique by using various proportions of
polymers such as xanthan gum or pectin, HPMC-K4M, carbopol-974P, and
with ethyl cellulose & magnesium sterate were used as an impermeable &
backing membrane respectively. The tablets were prepared by involving two
consecutive steps. In the first step, the mucoadhesive layer was prepared by
weighing accurately all the ingredients as shown in Tables 6.4, 6.5, 6.6 &
6.7 tablets incorporated with drug and mixed thoroughly in a glass mortar
for 15 min. Then this mixture was compressed using an 10-mm-diameter
die in the 10-station Rotary tablet punching machine (Chamunda Pharma
Pvt Ltd, Ahmadabad), followed by second step, after compression of the
adhesive core layer the upper punch was raised and ethyl cellulose and
magnesium stearate were added on the above compact and then again
compressed for the backing layer.
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The same procedure was adopted for the preparation of mucoadhesive
sustained release buccal tablets of Hydralazine HCl.
Table.6.4 Composition variables of nifedipine buccal tablets using xanthan gum