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

Authors

  • Bahar Darsazan Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Alireza Shafaati Department of Pharmaceutical Chemistry School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Afshin Zarghi Department of Pharmaceutical Chemistry School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Seyed Alireza Mortazavi Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

DOI:

https://doi.org/10.18433/jpps29394

Abstract

Purpose: 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. Methods: 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). Results: 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). Conclusion: These results suggest that the adefovir-CPC ion-paired system has potential for improving the permeation of adefovir across the intestinal membrane.

 

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Author Biography

Seyed Alireza Mortazavi, Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Professor of Pharmaceutics(Ph.D)

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Published

2018-05-16

How to Cite

Darsazan, B., Shafaati, A., Zarghi, A., & Mortazavi, S. A. (2018). Evaluation of Ion-pair Formation of Adefovir to Improve Permeation across Artificial and Biological Membranes. Journal of Pharmacy & Pharmaceutical Sciences, 21(1), 160–170. https://doi.org/10.18433/jpps29394

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Section

Review Articles