An investigation on thermal behaviour of Sevelamer Carbonate and non-isothermal decarboxylation kinetics using TGA to obtain activation energy and pre-exponential factor

Abstract

Sevelamer carbonate (SC) is a phosphate binder used to treat chronic kidney disease patients to remove excess phosphate. It is an insoluble drug and thus cannot be absorbed into the systemic circulation, so the in vivo bioequivalence studies cannot be performed. The USFDA, therefore, recommends in vitro phosphate binding tests and API-sameness tests to show the interchangeability of generic variants of the sevelamer carbonate tablets. The API-sameness mentions a variety of physicochemical characteristics including carbonate content. In this work, we studied the decarboxylation characteristics using thermal techniques (DSC & TGA). We have determined the activation energy and pre-exponential factor (Arrhenius parameters-Ea and A) that of the decarboxylation using nonisothermal kinetics of decarboxylation in combination with a well-accepted Coats-Redfern model-fitting method. A total of 13 different models were tested of solid-state reaction in which the second-order model suits best with an excellent correlation of 0.9926. The resultant values of the Ea and A are 25 kcal/mol and 1.23007 × 1012 Sec-1, respectively. The comparison of decarboxylation activation energy values may offer additional assurance on the API-sameness, in addition to comparing carbonate content alone.