title: Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and Sevelamer Carbonate.
abstract: The objective of this project is to develop an in vitro approach that can be used to determine the phosphate binding capacity of sevelamer hydrochloride and carbonate for both drug products and active pharmaceutical ingredients (APIs). A simple and efficient inductively coupled plasma spectrometer method for analysis of phosphate at physiologically relevant pH conditions has been developed and validated. The method addresses each of the analytical validation characteristics such as linearity, accuracy, precision, stability, and selectivity, and meets the acceptance criteria defined in the United States Food and Drug Administration guidance (Food and Drug Administration, Center for Drug Evaluation and Research. 2001. Guidance for industry-Bioanalytical method validation, May). The in vitro phosphate binding efficacies were systematically evaluated and compared for two drug products and two APIs. The phosphate binding profiles appeared similar between the drug products. Under all conditions, the sevelamer-phosphate binding reached equilibrium at 6 h. The 90% confidence interval for the k2 ratio (sevelamer carbonate vs. sevelamer hydrochloride) was well within 80%-125% under all pH conditions. However, the k1 ratio varied, indicating that there exists difference in the binding affinity. Our findings will be useful in assisting with "in vivo" biowaiver for the approval of generic sevelamer drug products.
authors.affiliation: Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Life Science Building 64, Silver Spring, Maryland 20993. Electronic address: yongsheng.yang@fda.hhs.gov.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Life Science Building 64, Silver Spring, Maryland 20993.
authors.forename: Adil
authors.initials: A
authors.lastname: Mohammad
authors.affiliation: Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Food and Drug Administration, Life Science Building 75, Silver Spring, Maryland 20993.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Berendt
authors.affiliation: Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Life Science Building 64, Silver Spring, Maryland 20993.
authors.forename: Alan
authors.initials: A
authors.lastname: Carlin
authors.affiliation: Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Life Science Building 64, Silver Spring, Maryland 20993.
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Life Science Building 64, Silver Spring, Maryland 20993.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Faustino
mesh_terms: D002614:Chelating Agents / Q000737:chemistry* / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000592:standards; D010602:Pharmacopoeias as Topic / Q000592:standards*; D000069603:Sevelamer / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D000069603:Sevelamer
keywords: absorption; bioequivalence; drug interaction; inductively coupled plasma; kinetics; langmuir equation; phosphate binding; polymeric drugs; sevelamer