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Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-β-cyclodextrin.

Anroop B Nair1, Mahesh Attimarad, Bandar E Al-Dhubiab

  • 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University , Al-Ahsa , Kingdom of Saudi Arabia and.

Drug Delivery
|November 13, 2013
PubMed
Summary

Developing an acyclovir-hydroxypropyl-β-cyclodextrin inclusion complex significantly enhanced oral bioavailability. This novel formulation offers a promising approach for effective oral acyclovir therapy against herpes viruses.

Keywords:
Acyclovirbioavailabilitydissolutionhydroxypropyl-β-cyclodextrinpharmacokinetics

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Area of Science:

  • Pharmaceutical Sciences
  • Drug Delivery Systems
  • Medicinal Chemistry

Background:

  • Acyclovir's therapeutic efficacy is hindered by poor oral bioavailability due to low aqueous solubility and permeability.
  • Enhancing acyclovir's oral delivery is crucial for effective treatment of herpes viral infections.

Purpose of the Study:

  • To develop and evaluate an inclusion complex of acyclovir with hydroxypropyl-β-cyclodextrin (HPβCD) to improve its oral bioavailability.
  • To investigate the in vitro and in vivo performance of the acyclovir-HPβCD complex.

Main Methods:

  • Acyclovir-HPβCD inclusion complex was prepared using the kneading method (1:1 mole ratio).
  • Characterization involved Fourier transform infrared spectroscopy, differential scanning calorimetry, and NMR spectroscopy.
  • In vitro dissolution studies and in vivo pharmacokinetic evaluation in a rat model were conducted.

Main Results:

  • Phase solubility studies confirmed complex formation with increased acyclovir solubility and a high stability constant.
  • Characterization confirmed the formation of the acyclovir-HPβCD inclusion complex.
  • The inclusion complex exhibited rapid acyclovir release (90.05% dissolution efficiency in 30 min) and significantly increased in vivo oral bioavailability (∼160% relative bioavailability).

Conclusions:

  • The acyclovir-HPβCD inclusion complex demonstrates superior in vitro dissolution and in vivo oral absorption compared to a physical mixture.
  • This complex represents a promising strategy for enhancing acyclovir's oral bioavailability for effective herpes virus treatment.