The influence of physical division of tablets on the variability of release kinetics of gliclazide.

Abstract: Tablets are often used in splitting process when the appropriated, registered dose is not available on the market or patients exhibit swallowing difficulties caused by the size of the tablet. The aim of the work was to assess the impact of physical division of tablets on the kinetics of in vitro gliclazide release from the intact and divided tablets. Gliclazide was released from prolonged release tablets containing 30 or 60 mg of the drug into a phosphate buffer, pH 7.4 and the amount of the drug in acceptor fluid was determined by UV-Vis spectrophotometry. The dissolution profiles were fit to zero- and first-order kinetics as well as to the Korsmeyer-Peppas equation. The largest discrepancy in the values of rate constants was obtained in the case of the release of gliclazide from intact and from splitting tablets using zero- and first-order kinetics. The values of the rate constants k₀ obtained from the release of the drug from the intact tablets and from fragments with a dose of the drug of 30 mg were (4.2 ± 0.1) × 10^-5 g min^-1 and (5.8 ± 0.1) × 10^-5 g min^-1, respectively, and k₁ were (2.3 ± 0.1) × 10^-3 min^-1 and (4.7 ± 0.6) × 10^-3 min^-1, respectively. These discrepancies were confirmed by the value of f₂ coefficient that was 45.9. The results suggest that physical division of tablets accelerate the release of gliclazide from its prolonged form.

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