Pharmaceutica Analytica Acta

In vitro permeability and solubility study of mefl oquine hydrochloride according to the Biopharmaceutics Classifi cation System (BCS) guidelines

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

Hao Cheng, Blair DeFulvio, Paula Kardos, Kathryn Weinstein, Lisa Murray, Sid Bhoopathy, and Ismael Hidalgo

Posters: PAA

Abstract:

Mefl oquine is a novel compound for the treatment of malaria; however, absolute oral bioavailability is unknown since an IV dosage form is not available. Th is study intends to classify mefl oquine according to the Biopharmaceutics Classifi cation System (BCS) guidelines issued by the FDA. Studies of mefl oquine to date have not conducted a thorough investigation of its BCS classifi cation, and the confl icting results suggest class I, II, or IV, partially due to inconsistent measurements of in vitro absorption behavior. Th e results presented here will provide BCS-relevant evidence of the absorption and permeability of mefl oquine. Th e permeability of mefl oquine was assessed in vitro using uni-directional permeability assays and will be assessed using bi-directional permeability assays with and without a pH gradient in a Caco-2 cell monolayer system, which has been fully validated at Absorption Systems. Minoxidil, a high permeability internal standard, and atenolol, a reference for monolayer integrity, were included in the unidirectional permeability experiment. Th e apparent permeability coeffi cient (P app ) of mefl oquine was lower than that of minoxidil, with and without an apical-to-basolateral (A-B) pH gradient. Th is suggests that mefl oquine is a low permeability drug according to BCS classifi cation. Th e recovery was approximately 50%, and there was no non-specifi c binding, indicating signifi cant cell accumulation. In bidirectional testing, the effl ux ratio (P app B-A/P app A-B) will be calculated to determine the role of active transport in permeation. Further, the aqueous solubility of mefl oquine will be assessed using the shake-fl ask method at pH 1.0, 3.0, 5.0 and 7.5.

Biography :

Absorption Systems, founded in 1996, assists pharmaceutical, biotechnology, and medical device companies in identifying and overcoming ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) barriers in the development of drugs, biologics, and medical devices. The company?s mission is to continually develop innovative research tools that can be used to accurately predict human outcomes or to explain unanticipated outcomes when they occur. Absorption Systems has facilities near Philadelphia, PA, and in San Diego, CA, and serves customers throughout the world. For information on the company?s comprehensive contract services and applied research programs, please visit www.absorption.com.