Formulation and physicochemical characterization of chitosan/acyclovir co-crystals

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Acyclovir (ACV) is a crucial antiviral medication with limited bioavailability.
• Improving ACV dissolution rate and bioavailability is essential for enhanced therapeutic efficacy.

Purpose of the Study:

• To investigate the effect of chitosan on the dissolution rate and bioavailability of acyclovir through co-crystal formation.
• To characterize the physicochemical properties and in vitro drug release of acyclovir-chitosan co-crystals.

Main Methods:

• Co-crystallization of acyclovir with varying concentrations and molecular weights of chitosan using a simple solvent change method and sodium citrate.
• Characterization of co-crystals including drug content, particle size, thermal analysis (DSC), IR spectroscopy, surface morphology (SEM), in vitro drug release studies, and physical stability testing.

Main Results:

• Co-crystal formation was successful, with practical yield inversely proportional to chitosan concentration.
• Drug content was uniform across batches. In vitro drug release was slower for co-crystals compared to pure acyclovir.
• Chitosan addition led to reduced drug crystallinity, altered surface morphology, and evidence of drug-chitosan interaction via IR spectroscopy.
• Optimized co-crystals demonstrated good physical stability for three months under accelerated conditions (40°C, 75% RH).

Conclusions:

• Chitosan co-crystallization alters acyclovir's physicochemical properties, including crystallinity and surface morphology.
• While initial dissolution rate was reduced, the observed changes suggest potential for improved bioavailability and enhanced physical stability of acyclovir.
• Further in vivo studies are warranted to confirm the bioavailability enhancement of these acyclovir-chitosan co-crystals.