Stability and bioavailability of diltiazem/polyethylene oxide matrix tablets

<p>The aim of this study was to prepare and evaluate <i>in vitro</i> and <i>in vivo</i>; Diltiazem-Hydrochloride (DTZ) in sustained-release matrix tablets. Stability of DTZ tablets prepared with polyethylene oxide (MWs 900 000, 4 000 000, and 8 000 000) with or without addition of electrolytes was carried-out for 1-month, under short-term storage at 40 °C/75% RH. Stability was evaluated by DTZ content, DSC and drug release using the Flow-Through Cell (USP # IV). The majority of stored tablets were stable for 1-month under short-term storage with respect to DTZ content and drug release. DSC curves of stored samples showed appearance of new exothermic peak after 1-month storage at 40 °C/75% RH, which was not observed after 5 years storage at room temperature. A selected formula was tested <i>in vivo</i> against reference product on eight healthy human volunteers. DTZ-plasma profiles were different between the two formulae. However, no statistically significant differences were detected between <i>C</i>_max, AUC_0–48 and AUC_0–∞. The two products were therapeutically in-equivalent, as 90% confidence intervals “T/R” were 88.82–205.76, 91.40–139.94, and 93.73–134.97 for <i>C</i>_max, AUC_0–48 and AUC_0–∞, respectively. This study highlighted possible differences observed between the two regimes frequently applied for stability testing.</p