Amalgamation of QbD and Alcohol Induced Dose Dumping Studies on Diltiazem Hydrochloride Modified Release Tablets

Background: Alcohol induced dose dumping is a noteworthy question in designing of modified release dosage forms and it led the marketed products withdrawal by regulatory agencies. Diltiazem HCl is a highly watersoluble drug and may undergo faster dissolution in presence of alcohol. The purpose of the present study was to develop extended-release tablets of Diltiazem HCl tablets by direct compression method having robustness in hydro-alcoholic media. Materials and Methods: Using QbD approach, lubricants and polymer as CMAs and drug release as CQAs were identified and further optimization was done by employing 32 factorial design. The extended-release tablets were evaluated for hardness, friability, weight variation and dissolution study was performed in 40% Alcoholic Phosphate buffer pH 5.8. Results: The scientific finding reveals that the concentration of HPMC K-100M DC (12%) and xanthan gums (12%) are capable of providing extended release of drug till the end of 12 hr in pH 5.8 phosphate buffer as well as in 40% Alcoholic Phosphate buffer pH 5.8. Conclusion: These results showed a robust in-vitro drug release profile when exposed to hydro-alcoholic media till 12 hr. Formulation was subjected to accelerated condition for stability testing and was found satisfactory.