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  • Evaluation of Ion-pair Formation of Adefovir to Improve Permeation across Artificial and Biological Membranes.

Evaluation of Ion-pair Formation of Adefovir to Improve Permeation across Artificial and Biological Membranes.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques (2018-05-24)
Bahar Darsazan, Alireza Shafaati, Afshin Zarghi, Seyed Alireza Mortazavi
ABSTRACT

Adefovir is an antiviral drug that exhibits high hydrophilic properties and negligible bioavailability (less than 12%). It is only applied in the form of the ester prodrug adefovir dipivoxil (ADV). The oral bioavailability of ADV is limited (32% to 45%) by its low permeability (Class 3) and biological conversion of the prodrug to adefovir. Ion-pair formation is considered as an alternative approach to a covalent prodrug (ADV) to enhance intestinal permeation of adefovir. The effect of various counter-ions (anionic, cationic and two quaternary ammonium salts) on the lipophilicity of adefovir was investigated by means of the n-octanol/buffer partitioning system, an in vitro transport model (PAMPA) and a biological membrane (everted gut sac). Quaternary ammonium salts, cetylpyridinium chloride (CPC) and cetrimide enhanced the lipophilicity of adefovir 136- and 87-fold, respectively. The apparent permeability of adefovir in combination with CPC (counter-ion) was 2.5-fold greater than ADV permeability in the PAMPA model. The apparent permeability of adefovir-CPC (counter-ion) was 1.3-fold greater than that of adefovir dipivoxil permeability in a biologic membrane (everted gut sac). These results suggest that the adefovir-CPC ion-paired system has potential for improving the permeation of adefovir across the intestinal membrane. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Adefovir, ≥98% (HPLC)