DISSOLUTION INSTABILITY OF ENCAPSULATED MARKETED TABLETS

For blinding purposes, 20 mg potency marketed tablets with some lactos e monohydrate were encapsulated in size # 0 blue opaque capsule shells . After prolonged room temperature storage in HDPE bottles containing cotton and heat activated film seal, some of the capsule lots showed s lower dissolution. No loss in potency was observed in these lots. When the contents of the capsules exhibiting the slower dissolution were t ransferred into fresh capsule shells, the original dissolution rate wa s observed. However, when aged tablet and fresh lactose monohydrate we re transferred into the aged capsule shells, slower dissolution was ob served. These observations indicated that the changes occurring in the capsule shells, rather than the capsule contents, were responsible fo r the decrease in dissolution. When the slow-dissolving capsules and ' as is' tablets were analyzed by HPLC, a peak corresponding to butylate d hydroxytoluene (BHT) was observed. This BHT was probably an impurity in butylated hydroxyanisole (BHA), which was used in the marketed tab let formulation as an antioxidant. The amount of BHT detected in the e ncapsulated tablet formulation was significantly lower than the amount detected in 'as is' marketed tablets. BHT can degrade in the presence of oxygen and moisture to form 2,6-di-tert-butyI-4-hydroxy-benzaldehy de as the main degradant product. It is hypothesized that this aldehyd e product cross linked the gelatin of the capsule shell resulting in t he observed decrease in the dissolution of the encapsulated product. O n the other hand, the encapsulated lot showing no decrease in dissolut ion showed comparatively less BHT, and the amount of BHT detected in c apsules and 'as is' tablets were not significantly different. Copyrigh t (C) 1996 Elsevier Science B.V.