Formulation and In vitro/In vivo evaluation of esomeprazole enteric coated minitablets

The objective of this study was to develop Esomeprazole solid dosage form as minitablets. The effect of coating thickness and percentage of fast disintegrants on the in vitro and in vivo performance of minitablets were studied. Two formulae (A1&B1) of the same core composition with different coat thickness were prepared initially. The in vivo study of A1 and B1 versus the originator revealed that their rate of dissolution was not enough to achieve bioequivalence with respect to Cmax, in spite of achieving acceptable extent of absorption. Therefore one of the formulas (A1) was modified to C1, by keeping the same coat thickness and increasing the percentage of disintegrant to enhance drug release rate during absorption phase. This modification increased in the dissolution rate as indicated by a higher dissolution efficiency (DE) for C1 than A1 and B1. A good correlation between DE and rate of absorption for A1, B1 and C1 was observed. In vivo studies under fasting conditions carried on 22 subjects revealed that the minitablets and Nexium were bioequivalent. Fed study was conducted on 16 subjects, showed that there was a significant delaying effect of food on drug absorption from minitablets.

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