Comparison Study of Grinding and Slurry Method on Physicochemical Characteristic of Acyclovir – Succinic Acid Cocrystal

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-raydiffraction (PXRD), differential scanning calorimetry, Fourier transform infrared (IR) spectroscopy, scanning electron microscope (SEM), anddissolution 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 themelting point of the constituent materials (ACV 253.53°C and SA 187.29°C). PXRD diffractogram showed that cocrystal with grinding method exhibitednew diffraction peaks at angle 2θ=8.92°, 16.24°, and 17.14°, while PXRD diffractogram of cocrystal with slurry method exhibit new diffraction peaksat angle 2θ=16.25°, and 19.63°. Characterization with IR spectroscopy showed the disappearance of transmission peaks at 3441cm disappearance ofC=O stretch at 1584cm and 1612cm. Dissolution efficiency of each treatment group calculated the efficiency of dissolution in 15th minutes, grindingmethod cocrystal with grinding time 15 minutes give the dissolution efficiency were 54.23%. Slurry method cocrystal with solvent concentration12 ml/g gives the high value of the dissolution efficiency is 74.36%. SEM micrographs showed that cocrystals prepared by solvent evaporation methodhave 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 cocrystalsof ACV-SA exhibited different physicochemical characteristics as compared to the constituent materials. The formed cocrystals prepared by slurrymethod have a high intensity of diffraction peak on X-ray diffraction and highest dissolution efficiency at 15 minutes rather than grinding methodcocrystal.Keywords: Cocrystal, Acyclovir, Succinic acid, Grinding, Slurry, Powder X-ray diffraction, Fourier transform infrared, Dissolution rate.

Screening and Preparation of Cocrystals: A Comparative Study of Mechanochemistry vs Slurry Methods

“…This study herein does not address other factors that are relevant from a practical utility perspective, including crystallinity, particle size, and bulk purity, each of which can impact dissolution rate and tabletability. 72 For example, Rahman and co-workers 73 compared the dissolution rate of an acyclovir-succinic acid cocrystal made via either slurrying or grinding. They reported that the cocrystal formed by slurrying exhibited a faster dissolution rate compared to the poorly crystalline product afforded by grinding.…”

Cocrystals: A Complete Review on Conventional and Novel Methods of Its Formation and Its Evaluation

“…It is known to be ecofriendly method for industrial-level production due to less amount of solvent used. The process does not also depend on the temperature, and more importantly, it diminishes the chances of unwanted solvate formation, adefovir dipivoxil-glutaric acid cocrystal [27] and quercetinsuccinic acid cocrystal improves solubility and dissolution rate by 1.62 and 1.25, respectively.…”

Co-Crystals of Carvedilol: Preparation, Characterization and Evaluation

“…fig. 4 (B)-(D) From XRD spectra it was observed and concluded that, the intensity and number of peaks were reduced in the XRD spectra of Carvedilol co-crystals compare to pure Carvedilol indicate that the reduction in crystallinity and formation of new bonding in the co-crystals This variation in the XRD pattern of pure Carvedilol and its Co-crystals due to changes in the crystal lattice structure of drug and conformer [19].…”