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Preparation and physicochemical characterization of acyclovir cocrystals with improved dissolution properties
Giovanna Bruni1, Mariarosa Maietta, Lauretta Maggi
1C.S.G.I., Department of Chemistry, Physical-Chemistry Section, University of Pavia, Pavia, Italy.
Journal of Pharmaceutical Sciences
|September 14, 2013
Summary
New cocrystals of acyclovir (ACV) with glutaric and fumaric acids were developed. The fumaric acid cocrystal (AFA1:1) significantly enhanced ACV dissolution rates, improving its potential for better drug delivery.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Drug Delivery
Background:
- Acyclovir, a key antiviral, suffers from poor water solubility and low oral bioavailability.
- Its absorption is limited by solubility (0.2 g/100 mL) and a short half-life (~3 h).
- High doses are required, impacting patient compliance and treatment efficacy.
Purpose of the Study:
- To enhance acyclovir's solubility and dissolution properties.
- To develop novel cocrystals of acyclovir with glutaric acid and fumaric acid.
- To characterize the cocrystals and evaluate their dissolution behavior.
Main Methods:
- Cocrystal formation using cogrinding method.
- Characterization via thermal analysis, FTIR, XRPD, ssNMR, and SEM-EDX.
- Solubility and intrinsic dissolution rate (IDR) studies at different pH.
Main Results:
- Two cocrystals, AGA1:1 (acyclovir:glutaric acid) and AFA1:1 (acyclovir:fumaric acid), were successfully synthesized.
- AFA1:1 showed a slight increase in equilibrium solubility compared to acyclovir.
- Both cocrystals exhibited significantly faster intrinsic dissolution rates (IDR), especially AFA1:1, which dissolved completely within 10 minutes.
Conclusions:
- Cocrystal formation is a viable strategy to improve acyclovir's dissolution properties.
- The AFA1:1 cocrystal demonstrates superior dissolution performance compared to acyclovir and AGA1:1.
- This enhanced dissolution may lead to improved oral bioavailability and therapeutic efficacy of acyclovir.
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