Determination of density.
Density was determined using the liquid-displacement method (19, 20). Benzene, in which the tablet was insoluble, was used
as intrusion in the glass pycnometer. Density of the optimized formulation was 0.978 g/cm–1.
Table V: Medium uptake by the optimized formulation.
The swelling properties of the formulation can be determined through various techniques (21). The medium uptake was evaluated
using simulated gastric fluid as a medium for 2 h (see Table V). The dimensional changes are summarized in Table VI.
Table VI: Swelling characteristics (i.e., dimensional changes).
In vitro dissolution study.
The cumulative drug release from each formulation was assessed using 900 mL of dissolution media (0.1 N HCl) in Apparatus
2 of USP XXI (15), with a paddle-rotation speed of 50 rpm. Aliquots of 10 mL were withdrawn after every hour. These aliquots were
filtered through a 0.45-μm membrane filter and analyzed by measuring the absorbance, using the 0.1 N HCl as reference solution,
at 221 nm (15). The absorbance values were transformed to concentration by reference to a standard calibration curve obtained
2 = 0.999).
Figure 1: Release profiles of the formulations F2, F3, F4, and F8. See Table III for the batch formulations’ compositions.
The dissolution test was performed in triplicate for each batch, and t
80 was calculated. The release rates of various formulations are shown in Figures 1 and 2, and release rates and t
80 are summarized in Tables VII and VIII, respectively. The responses studied included the time needed for 50% of the drug to
50), the diffusional exponent (n) that characterized the release mechanism, and the percent friability of the tablets. Analysis of variance indicated that
the release rate (T
50) was affected by the ratio of HPMC grades, the amount of Carbopol and sodium bicarbonate, and two-way and three-way interactions.
The ratio of HPMC grades, the amount of Carbopol and sodium bicarbonate, the interactions between HPMC and Carbopol and HPMC
and sodium bicarbonate, and also three-way interactions significantly affected the diffusional exponent (n). Tablet friability was affected significantly by all three factors.
Figure 2: Release profiles of the formulations F1, F5, F6, and F7. See Table III for the batch formulations’ compositions.
The formulation with the best release characteristics was F8. Sustained release of the optimized formulation was achieved
over a period of 24 h. An average of 95–99% of the drug was released during this period. All the factors of formulation except
F7 were insignificant (P > 0.05). From these results, it can be inferred that because all quadratic terms of the main factors and interactions were
of little significance, a reasonably linear relationship linked both factors and the response, though interaction between
main effects was significant.
Table VII: Dissolution studies of various batch formulations.
For the drug-content estimation, 20 tablets of each formulation were added to 100 mL of 0.1 N HCl after triturating the tablets,
followed by stirring for 30 min. The solution was filtered through a 0.45-μm membrane filter and diluted, and the absorbance
of the resulting solution was measured spectrophotometrically at 221 nm using 0.1 N HCl as a blank. The drug content was uniform
in all formulations.
Table VIII: t80 value of various formulations.
In vitro drug-release kinetic studies.
The kinetic model described drug dissolution from the solid dosage form, where the dissolved amount of drug was a function
of test time. To study the exact mechanism of drug release from the tablets, drug-release data were analyzed according to
zero order, first order, Higuchi square root, and the Korsmeyer–Peppas model (22–25). The criteria for selecting the most
appropriate model were chosen on the basis of the goodness-of-fit test.