Journal of Bioequivalence & Bioavailability

Abstract

In vitro Bioequivalence Studies in Tablet Formulation Containing 625 mg of Colesevelam Hydrochlorides

Gulcin Tok, Ediz Yildirim and Ali Turkyilmaz

Colesevelam hydrochloride is a second generation bile acid sequestrant that is used principally for treatment of elevated LDL cholesterol. Additionally, it is indicated to improve glycemic control in adults with type 2 diabetes mellitus. Colesevelam hydrochloride is an insoluble, non-absorbed polymer that binds bile acids in the intestine, impeding their reabsorption. Because the drug is not absorbed into the systemic circulation, pharmacokinetic information is not available. The present abstract focuses on the study of in vitro BE in tablet formulation containing 625 mg of Colesevelam hydrochloride. Bile acid salts of Glycocholic Acid (GC), Glycochenodeoxycholic Acid (GCDC) and Taurodeoxycholic Acid (TDC) were used in vitro BE studies. The binding capacity HPLC method was developed and validated for these bile acid salts. The equilibrium binding study that is the pivotal BE study and in vitro kinetic binding study that is the support the pivotal equilibrium binding study was repeated twelve times. In the in vitro equilibrium binding studies, the Langmuir binding constants k1 (affinity) and k2 (capacity) were calculated for the three salts, individually and combined (GC+GCDC+TDC) using both nonlinear Langmuir equation and linear Langmuir equation for the test and reference products. The calculated capacity constant (k2), the more important parameter, were obtained very similar between test and reference products in the 90% confidence interval and acceptance criteria of 80% to 120%. The test/reference ratio for capacity constant, k2, was obtained 0.918 and 0.922 using equation 1 and 2 for total bile acid salts from the without acid pre-treatment equilibrium binding study and 0.948, 0.953 using equation 1 and 2 for total bile acid salts from the with acid pre-treatment equilibrium binding study.