COMPARISON STUDY OF GRINDING AND SLURRY METHOD ON PHYSICOCHEMICAL CHARACTERISTIC OF ACYCLOVIR – SUCCINIC ACID COCRYSTAL
2017
ABSTRACT Objective: This study aimed to compare the characteristics of acyclovir (ACV)-succinic acid (SA) cocrystal with grinding and slurry method. Methods: Cocrystals were prepared using grinding and slurry methods. Physicochemical characterizations were performed using powder X-ray diffraction (PXRD), differential scanning calorimetry, Fourier transform infrared (IR) spectroscopy, scanning electron microscope (SEM), and dissolution test. Results: The study revealed that cocrystal of ACV-SA showed a decrease in the melting temperature, i.e., 175.10°C, respectively, in comparison with the melting point of the constituent materials (ACV 253.53°C and SA 187.29°C). PXRD diffractogram showed that cocrystal with grinding method exhibited new diffraction peaks at angle 2θ=8.92°, 16.24°, and 17.14°, while PXRD diffractogram of cocrystal with slurry method exhibit new diffraction peaks at angle 2θ=16.25°, and 19.63°. Characterization with IR spectroscopy showed the disappearance of transmission peaks at 3441cm disappearance of C=O stretch at 1584cm and 1612cm. Dissolution efficiency of each treatment group calculated the efficiency of dissolution in 15th minutes, grinding method cocrystal with grinding time 15 minutes give the dissolution efficiency were 54.23%. Slurry method cocrystal with solvent concentration 12 ml/g gives the high value of the dissolution efficiency is 74.36%. SEM micrographs showed that cocrystals prepared by solvent evaporation method have differences crystal form at magnification 5000× magnification compared to pure ACV and physical mixture. Conclusion: The study concluded that cocrystals of ACV-SA were successfully formed using grinding and slurry methods. The formed cocrystals of ACV-SA exhibited different physicochemical characteristics as compared to the constituent materials. The formed cocrystals prepared by slurry method have a high intensity of diffraction peak on X-ray diffraction and highest dissolution efficiency at 15 minutes rather than grinding method cocrystal. Keywords: Cocrystal, Acyclovir, Succinic acid, Grinding, Slurry, Powder X-ray diffraction, Fourier transform infrared, Dissolution rate.
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