Enhanced solubility of microwave-assisted synthesized acyclovir co-crystals

This study aimed to enhance the kinetic solubility of ACV by using microwave-assisted technique to form ACV co-crystals and overcome its limited aqueous solubility. Co-crystallization is one of the commonly used techniques to improve the dissolution rates of active pharmaceutical ingredients (APIs). Acyclovir (ACV) has a limited efficacy due to its low oral bioavailability resulted from its poor aqueous solubility and permeability. Acyclovir co-crystals were formulated by microwave assisted solvent extraction (MASE) in equimolar ratio of 1:1 with different co-formers. Physical and structural characterization by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy were performed. Further evaluation of the co-crystals solubility, dissolution rate and content were carried out using the ultraviolet (UV) spectrophotometry. Co-crystals of acyclovir and tartaric acid (ACV-TA) in equimolar ratio of 1:1 produced by MASE using the glacial acetic acid as a solvent were more soluble compared to plain drug. The dissolution rate was increased from only 59.0% of pure acyclovir up to 85.0% of ACV co-crystals within 1 hour. DSC and PXRD patterns of co-crystals were distinguished from that of individual components. The UV-spectroscopic analysis represented 62.5% of acyclovir in the co-crystals, which was directly related to the theoretical percentage of the drug and its co-former (ACV: 60.01%, TA: 39.99%). This study revealed that the optimal ratio of the ACV-TA co-crystal is 1:1, which was successfully prepared using MASE technique. This method provides a promising alternative for enhancing the solubility of acyclovir with ultimately less time and solvent consumption.