The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations

Borbás, Enikő and Nagy, Zsombor Kristóf and Nagy, Brigitta and Balogh, Attila and Farkas, Balázs and Tsinman, Oksana and Tsinman, Konstantin and Sinkó, Bálint (2018) The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 114. pp. 310-317. ISSN 0928-0987

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Abstract

In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%. Changing the salt forming agent as well resulted in approximately 20% of flux reduction compared to the brand formulation. This significant difference was clearly shown in the published in vivo results as well. The use of additional lactose monohydrate in the formulation also leads to approximately 10% reduction in flux. The results show that by changing excipients, the dissolution of telmisartan was not altered significantly, but the flux through the membrane was found to be significantly changed. These results pointed out the limitations of traditional USP dissolution tests and emphasized the importance of simultaneously measuring dissolution and absorption, which allows the complex effect of formulation excipients on both processes to be measured. Moreover, the in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo bioequivalence study results.

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