EFFECT OF FORMULATION AND PROCESS VARIABLES ON DEGRADATION PRODUCTS OF LOVASTATIN IN TABLET DOSAGE FORM
Abstract
Objective: Quantification of degradation products in drug substances and products is the most challenging tasks in pharmaceutical industries
nowadays. Systematic study on the degradation products of lovastatin in compressed tablets has not been reported in the literature. The objective
of the present study is to investigate the effect of excipients and method of manufacturing on the degradation products of lovastatin in compressed
tablets manufactured by three different methods. The study also aims to evaluate the impact of aging and packaging material on the degradation
products.
Methods: Tablets of lovastatin were prepared by wet granulation, dry granulation and direct compression methods with different excipients. The
tablets were assayed by a validated HPLC method for lovastatin and its major degradation products initially and after 12 months period while storing
at 25±°C in glass bottles, Polyvinyl chloride/Aluminum foil blisters and Alu/Alu blisters.
Results: Results have shown that excipients and method of manufacturing influence the amounts of major degradation products hydroxyacid
lovastatin (HAL) and dehydrolovastatin (DHL) which were found in amounts of 0.67% and 0.45% in tablets compressed via wet-granulation, 0.42%
and 0.19% in tablet compressed via dry-granulation and 0.30% and 0.20% in tablets compressed via direct compression method respectively. The
tablets showed maximum stability in Alu/Alu packing followed by packing in glass bottles and PVC/Al. foil blisters, respectively.
Conclusion: This study concluded that lovastatin obtained from different sources have different degradation products showing that they are originated
from the manufacturing stage of the API. The varying contents of the degradation products in tablets manufactured by different methods initially and
with time indicate that the manufacturing process and excipients also have important role in generation of degradation products. Furthermore,
packaging material significantly affect the stability of the tablets during storage. Therefore, all these conditions and factors must be considered and
controlled during formulation, manufacturing, and storage of the compound and its formulated products.
Keywords: Lovastatin, Degradation products, Hydroxy acid lovastatin and dehydro lovastatin.
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