Evaluation of “In-Use” Stability Period of Lacidipine Tablets in Multi-dose Plastic Container-Closure

Abstract

Lacidipine (LCDP) is chemically a 1,4-dihydropyridine derivative and pharmacologically a “calcium channel blocker” used as an anti-hypertensive agent. Lacidipine is most sensitive to light and moisture, which is in line with the well-known sensitivity of the dihydropyridine class of compounds. In general, moisture protection can be obtained by packaging into moisture impermeable material, while light protection can be obtained by covering tablets with an opaque film coating.  But, when film-coated tablets are packed in High Density Polyethylene (HDPE) multi-dose plastic containers and closures, repeated opening and closing may pose a risk to their contents with regard to microbiological contamination and physicochemical degradation once the closure system has been breached. The continued integrity of the product in multi-dose containers after the first opening is an important quality issue.  Thus, the main objective of the present in-use stability study was to establish a period of time during which a multi-dose Lacidipine tablet product can be used whilst retaining quality within an accepted specification once the container is opened. The extent of drug product testing was established by assessing whether or not there was acceptable change, mainly in terms of impurities generated by different factors and microbial loads mainly in terms of bacteria/yeast/mould occurrence over the in-use stability or at the end of the in-use stability study period. Our results from drug assay, dissolution and impurity profile studies assessed as per the regulatory specifications suggest that the lacidipine product should be used within 4 weeks after opening of the container. The container should be closed tightly after each use to limit drug product degradation.