The Development of a Floating Drug-Delivery System for Metronidazole - Pharmaceutical Technology

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The Development of a Floating Drug-Delivery System for Metronidazole
The authors developed a metronidazole-based floating drug-delivery system to investigate the effect of rate-controlling polymers on release pattern and duration of buoyancy in matrix tablets.

Pharmaceutical Technology
pp. 41-44

Physical testing of the tablet. The tablets' thickness and diameter were measured with digital vernier calipers. Tablet hardness was determined at room temperature by diametric compression using a hardness tester (Veego Scientific Devices). The percentage friability of the tablets was determined using a tablet-friability apparatus (Veego Scientific Devices) operated at 25 rpm for 4 min. Tablets were weighed accurately, placed in the chamber and, rotated for 4 minutes (100 rotations). At the end of the run, the dust on the tablet was removed carefully, tablets were weighed accurately again, and the percent friability (f) was computed from the weight of the tablets before and after the test according to the following equation:

where W o and W are the weights of tablets before and after the test, respectively.

The bulk density of the powder, normally expressed as g/mL, was determined by dividing the weight of the powder by the volume it occupies. Tap density was determined by subjecting the powder in a graduated cylinder to 500 taps by the standardized US Pharmacopiea II tapping procedure (with VTAP MATIC-II, Veego) and using following equation:

The Hausner's ratio was determined as the ratio of the initial bulk volume to the tapped volume. The Carr's index was calculated using bulk and tapped densities data through the following equation:

Buoyancy of the tablet and floating properties. The tablets were placed in 900 mL of 0.1 N mol L−1 HCl solution, and floating properties were determined using USP dissolution test apparatus II (Electrolab and Veego) at 50 rpm and 37 0.5 C. The time required for the tablet to rise to the surface and float was taken as the floating lag time. The in vitro buoyancy was determined according to floating lag time and duration of floating viscosity.

Water uptake. Water uptake was determined in an acid medium of 0.1 N HCl (pH 1.2) and water at 37 0.5 C. The percentage of water uptake was calculated according to the following equation:

in which w t is the weight of the swollen tablet at time t, and w o is the initial weight of the tablet. The saturation time was obtained by determining the point at which no more water was taken up (i.e., 20–30 s). The swelling of the polymer depends on the rate of water penetration into the tablet. The water-penetration measurement was primarily used to evaluate polymer-penetration interactions that enable the tablet to dissolve (3).

In vitro drug-release studies. The in vitro release studies of metronidazole tablets were conducted using USP dissolution apparatus II (Electrolab and Veego). The dissolution testing was performed using 900 mL of 0.1 N HCL at 50 rpm and 37 0.5 C. A sample of the solution was withdrawn from the dissolution-testing apparatus every hour for 8 h, and the samples were replaced with fresh dissolution medium. The samples were diluted with 0.1 N HCl 55 times. Absorbance of these solutions was measured at 278 nm using a Shimadzu spectrophotometer.

Kinetic study. The in vitro release mechanism of drug from floating tablets was determined on the basis of theoretical dissolution evaluations including zero order, first order, Higuchi kinetic model and Korsmeyer–Peppas kinetic model with goodness-of-fit test.

Statistical analysis. Analysis of variance was applied to F1 through F9 to see whether release characteristics differed significantly (p ≤ 0.05) because of variation in polymer concentrations. Results showed that polymer-based formulations had significantly different release characteristics.


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