COMPARISON STUDY OF GRINDING AND SLURRY METHOD ON PHYSICOCHEMICAL CHARACTERISTIC OF ACYCLOVIR â€“ SUCCINIC ACID COCRYSTAL
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
Results: The study revealed that cocrystal of ACV-SA showed a decrease in the melting temperature, i.e., 175.10Â°C, respectively, in comparison with the
melting point of the constituent materials (ACV 253.53Â°C and SA 187.29Â°C). PXRD diffractogram showed that cocrystal with grinding method exhibited
new diffraction peaks at angle 2Î¸=8.92Â°, 16.24Â°, and 17.14Â°, while PXRD diffractogram of cocrystal with slurry method exhibit new diffraction peaks
at angle 2Î¸=16.25Â°, and 19.63Â°. 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 5000Ã— 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
Keywords: Cocrystal, Acyclovir, Succinic acid, Grinding, Slurry, Powder X-ray diffraction, Fourier transform infrared, Dissolution rate.
1. Allam AN, Naggar VF, El Gamal SS. Formulation and physicochemical characterization of chitosan/acyclovir co-crystals. Pharm Dev Technol 2013;18(4):856-65.
2. Biswas N. Solid forms and pharmacokinetics. In: Wouters J, Quere L, editors. Pharmaceutical Salts and Co-crystals. Cambridge: The Royal Society of Chemistry; 2012.
3. Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev 2007;59:617-30.
4. Bond AD. Fundamentals aspects of salts and co-crystals. In: Wouters J, Quere L, editors. Pharmaceutical Salts and Co-crystals. Cambridge: The Royal Society of Chemistry; 2012.
5. Bruni G, Maietta M, Maggi L, Mustarelli P, Ferrara C, Berbenni V, et al. Preparation and physicochemical characterization of acyclovir cocrystals with improved dissolution properties. J Pharm Sci 2013;102:4079-86.
6. Fabian L, Friscic T. Shape and polarity in co-crystal formation: Database analysis and experimental validation. In: Wouters J, Quere L, editors. Pharmaceutical Salts and Co-Crystals. Cambridge: The Royal Society of Chemistry; 2012.
7. Friscic T, Jones W. Application of mechanochemistry in the synthesis and discovery of new pharmaceutical forms: Co-crystals, salts, and coordination compounds. In: Wouters J, Quere L, editors. Pharmaceutical Salts and Co-Crystals. Cambridge: The Royal Society of Chemistry; 2012.
8. Gilmore CJ. X-ray diffraction. In: Storey RA, Ymen I, editors. Solid State Characterization of Pharmaceuticals. Chichester: Blackwell Publishing; 2011.
9. He G, Jacob C, Guo L, Chow PS, Tan RB. Screening for cocrystallization tendency: The role of intermolecular interactions. J Phys Chem B 2008;112:9890-5.
10. Hiendrawan S, Hartanti AW, Veriansyah B, Widjojokusumo E, Tjandrawinata RR. Solubility enhancement of ketoconazole via salt and cocrystal formation. Int J Pharm Pharm Sci 2015;7(7):160-4.
11. ICH. Validation of Analytical Procedures: Text and Metodology Q2 (R1). ICH Harmonised Tripartite Guideline; 2005.
12. Karki S, FÃ¡biÃ¡n L, Friscic T, Jones W. Powder X-ray diffraction as an emerging method to structurally characterize organic solids. Org Lett 2007;9:3133-6.
13. Kern A. Profile analysis. In: Clearfield A, Reibenspies J, Bhuvanesh N,
AQ3editors. Principles and Applications of Powder Diffraction. Chichester: Blackwell Publishing; 2008.
14. Masuda T, Yoshihashi Y, Yonemochi E, Fujii K, Uekusa H, Terada K. Cocrystallization and amorphization induced by drug-excipient interaction improves the physical properties of acyclovir. Int J Pharm 2012;422(1-2):160-9.
15. Oâ€™Neil A, Edwards H. Spectroscopic characterization. In: Storey RA, Ymen I, editors. Solid State Characterization of Pharmaceuticals. Chichester: Blackwell Publishing; 2011.
16. Qiao N, Li M, Schlindwein W, Malek N, Davies A, Trappitt G. Pharmaceutical cocrystals: An overview. Int J Pharm 2011;419(1-2):1-11.
17. Rodriguez-Hornedo Z, Nehm SJ, Jayasankar A. Cocrystal: Design, properties and formation mechanisms. In: Swabrick J, editor. Encyclopedia of Pharmaceutical Technology. 3rd ed., Vol. 3. United State of America: Informa Health Care; 2007.
18. Roy L, Lipert MP, Rodriguez-Hornedo N. Co-crystal solubility and thermodynamic stability. In: Wouters J, Quere L, editors. Pharmaceutical Salts and Co-Crystals. Cambridge: The Royal Society of Chemistry; 2012.
19. Sarkar A, Rohani S. Cocrystals of acyclovir with promising physicochemical properties. J Pharm Sci 2015;104:98-105.
20. Saunders M, Gabbott P. Thermal analysis-conventional techniques. In: Storey RA, Ymen I, editors. Solid State Characterization of Pharmaceuticals. Chichester: Blackwell Publishing; 2011.
21. Schultheiss N, Henck JA. Role of co-crystals in the pharmaceutical development continuum. In: Wouters J, Quere L, editors. Pharmaceutical Salts and Co-crystals. Cambridge: The Royal Society of Chemistry; 2012.
22. Schultheiss N, Newman A. Pharmaceutical cocrystals and their physicochemical properties. Cryst Growth Des 2009;9:2950-67.
23. Setyawan D, Sari R, Yusuf H, Primaharinastiti R. Preparation and characterization of artesunate-nicotinamide cocrystal by solvent evaporation and slurry method. Asian J Pharm Clin Res 2014;7(1):62.
24. Shah K, Borhade S, Londhe V. Utilization of co-crystallization for solubility enhancement of a poorly soluble antiretroviral drug â€“ ritonavir. Int J Pharm Pharm Sci 2014;6(2):556-8.
25. Sohn YT, Kim SH. Polymorphism and pseudopolymorphism of acyclovir. Arch Pharm Res 2008;31:231-4.
26. Sweetman SC, editor. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press Publishing; 2009.
27. Takata N, Shiraki K, Takano R, Hayashi Y, Terada K. Cocrystal screening of stanolone and mestanolone using slurry crystallization. Cryst Growth Des 2008;8(8):3032-7.
28. Thakuria R, Delori A, Jones W, Lipert MP, Roy L, RodrÃguez-Hornedo N. Pharmaceutical cocrystals and poorly soluble drugs. Int J Pharm 2013;453:101-25.
29. Tomaszewska I, Karki S, Shur J, Price R, Fotaki N. Pharmaceutical characterisation and evaluation of cocrystals: Importance of in vitro dissolution conditions and type of coformer. Int J Pharm 2013;453(2):380-8.
30. Yamashita H, Hirakura Y, Yuda M, Teramura T, Terada K. Detection of cocrystal formation based on binary phase diagram using thermal analysis. Pharm Res 2013;30(1):70-80.
31. Zaini E, Halim A, Soewandhi SN, Setyawan D. Peningkatan laju pelarutan trimetoprim melalui metode ko-kristalisasi dengan nikotinamida. J Farm Indones 2011;5(4):205-12.
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