Understanding Degradation Pathway of Poorly Stable Diltiazem Hydrochloride and Development of its Stabilized Controlled-release Tablets

Abstract

Diltiazem hydrochloride is a class -1 drug, as per the breast-conserving surgery (BCS) classification system, which is highly soluble and highly permeable. It is a poorly stable drug that poses many problems during formulation preparation. The stability of the final product is quite challenging. The API undergoes hydrolysis to form desacetyl-diltiazem. It is the major degradation impurity. Desacetyl-diltiazem exhibits only a quarter to half of the pharmacological activity as compared to diltiazem HCl. A correct understanding of the degradation pathway and usage of suitable excipients can provide a stable product with improved shelf life. During the course of various trials and application of factorial designing, an optimized composition for oral controlled release tablets of diltiazem HCl has arrived, suggesting that exposure to an aqueous medium for tablets granulation and eliminating the polyvinylpyrrolidone from the composition significantly improved the product stability and final tablets shelf life by not only maintaining the desired in-vitro drug release profile but also keeping the related substances (impurities level) at very low levels throughout the entire shelf life.