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

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.