Weight uniformity was determined with a digital balance (model 220BL, Shimadzu Corporation, Kyoto, Japan) according to the
official method (19). Tablet hardness and thickness were evaluated using a hardness tester (Scientific Engineering Corp., Delhi, India) and digimatic caliper (Mitutoyo Corp., Japan), respectively (20). For each batch, tablet friability was determined in an automated USP friabilator (model EF-2,
Electrolab (I) Ltd., Mumbai). Tablet content uniformity was computed from the assay values in 2% w/w solution of sodium lauryl
In vitro dissolution studies were carried out in triplicate for 45 min in USP dissolution-rate test Apparatus II (model TDT-06T,
Electrolab (I) Ltd., Mumbai), as per the official method (9). Dissolution media consisting of 900 mL of 2% w/w SLS in distilled
water was maintained at 37 ± 0.5 °C and a stirring speed of 50 rpm. Samples were withdrawn at time intervals of 15 min, filtered
through 0.45-μm filter, suitably diluted, and analyzed spectrophotometrically at 270 nm using 2% w/w solution of SLS as a
reagent blank. Percent dissolution efficiency at 45 min, used to compare the dissolution profiles of the model formulations,
was calculated using Equation 2:
in which Yt stands for percent of drug dissolved at time T and Y100 denotes 100 % dissolution (21). The integral representing the area under the dissolution curve between time zero and time
T was computed using Graph Pad Prism version 4.02 (GraphPad Software., San Diego, CA).
The targeted response parameters were statistically analyzed by applying one-way analysis of variance (ANOVA) at 0.05 level
in Design-Expert 7.1.3 demo version soft ware (Stat-Ease Inc.., Minneapolis, MN). Individual parameters were evaluated using the F test, and polynomial models of the form indicated in Equation 3 were generated for each response parameter.
in which Y is the level of the measured response, β0 is the intercept, and β1 to β5 are the regression coefficients. X1 and X2 stand for the main effects; X1 X2, X2X3, and X1X3 are the two-way interactions between the main effects, and X1X2X3 represents the three way interaction. Mathematical models containing only the significant terms were generated for each response
parameters using multiple linear regression analysis (MLRA) and ANOVA. The models generated were used to construct the three-dimensional
graphs in which response parameter Y was represented as a function of X. The effect of independent variables on each response also was visualized from the contour plots.
Validation of the mathematical models.
The mathematical models representing the response parameters were validated by developing a new formulation with a combination
of factors within the experimental domain (16). Constraints such as minimizing the disintegration time (DT) and maximizing
the wetting time (WT)and dissolution efficiency at 60 min (%DE60) were set to locate the optimum settings of the independent
variables in the new formulation. The new formulation was evaluated for the responses, and the experimental values obtained
were compared with those predicted by the mathematical models.