Gulcin Tok
Sanovel Pharmaceuticals, Turkey
Title: In-vitro bioequivalence studies in tablet formulation containing 625 mg of colesevelam hydrochloride
Biography
Biography: Gulcin Tok
Abstract
Colesevelam is a second generation bile acid sequestrant that is used principally for treatment of elevated LDL cholesterol. Additionally, Colesevelam is indicated to improve glycemic control in adults with type 2 diabetes mellitus. Colesevelam is an insoluble, non-absorbed polymer that binds bile acids in the intestine, impeding their reabsorption. Conventional in vivo bioequivalence (BE) study with pharmacokinetic endpoints such as Cmax and AUC is neither appropriate nor feasible for this locally acting drug. The present abstract focuses on the study of in vitro BE in tablet formulation containing 625 mg of Colesevelam HCl. Bile acid sodium salts of glycocholic acid (GCA), glycochenodeoxycholic acid (GCDA) and taurodeoxycholic acid (TDCA) 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 were repeated 12 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 linear Langmuir equation for the test and reference products. The calculated capacity (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 k2 was obtained within 0.82-1.07 from the equilibrium binding study for without acid pre-treatment and 0.96-1.08 from the equilibrium binding study for with acid pre-treatment.