• Roisah Nawatila Airlangga University
  • Agnes Nuniek W
  • Siswandono Siswodihardjo
  • Dwi Setyawan



Objective: This research aims to prepare cocrystal of acyclovir (ACV)-nicotinamide (NCT) by solvent evaporation with a variation of solvent (ethanol,
glacial acetic acid, and HCl 0.1 N) to improve the bioavailability of ACV as an antiviral drug.
Methods: Cocrystal were developed by solvent evaporation with 1:1 molar fraction, using variation of solvent such as ethanol, glacial acetic acid, and
HCl 0.1 N. Further, the prepared ACV-NCT cocrystal were characterized for differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD),
Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and in vitro dissolution.
Results: DSC thermogram showed that ACV-NCT cocrystal in ethanol and glacial acetic acid exhibited new endothermic peak at 221.16°C and
216.40°C, whereas no peaks were found for HCl 0.1 N. PXRD diffractogram showed that ACV-NCT cocrystal in ethanol exhibited new diffraction peaks
at 2θ 5.9°; 9.2°; dan 13.3°, whereas no peaks were found for glacial acetic acid and HCl 0.1 N. FT-IR characterization of ACV-NCT cocrystal in ethanol
showed disappearance of transmission peaks at 3373/cm indicating the loss of NH bands of NCT. Furthermore, C=O of ACV and NCT were observed at
1693/cm, and 1666/cm indicated a formation of hydrogen bonding between ACV and NCT. SEM micrographs showed that cocrystals have a different
shape compared to ACV and NCT. DE15 showed that there was a significant increase of ACV-NCT cocrystal dissolution rate in ethanol compared to the
physical mixture and ACV.
Conclusion: The study concludes that ACV-NCT cocrystal in ethanol were successfully formed and the dissolution rate of ACV can increase significantly
Keywords: Cocrystallization, Solvent, Acyclovir, Nicotinamide, Solvent evaporation.



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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(11):4079-86.

Sarkar A, Rohani S. Cocrystals of acyclovir with promising physicochemical properties. J Pharm Sci 2015;104(1):98-105.

Yan Y, Chen JM, Lu TB. Simultaneously enhancing the solubility and permeability of acyclovir by crystal engineering approach. CrystEngComm 2013;15:6457-60.

Zaini E, Halim A, Soewandhi SN, Setyawan D. Peningkatan laju pelarutan trimetoprim melalui metode ko-kristalisasi dengan nikotinamida. J Farmasi Indones 2011;5(4):205-12.

Yadav S, Gupta PC, Sharma N, Kumar J. Cocrystals: An alternative approach to modify physicochemical properties of drugs. Int J Pharm Chem Biol Sci 2015;5(2):427-36.

Zalte AG, Saudagar RB. Advanced techniques in preparation of cocrystals. Int J Sci Prog Res 2015;12(1):32-5.

Kotak U, Prajapati V, Solanki H, Jani G, Jha P. Co-crystallization technique its rationale and recent progress. World J Pharm Pharm Sci 2015;4(4):1484-508.

Fukte SR, Wagh MP, Rawat S. Coformer selection: An important tool in cocrystal formation. Int J Pharm Pharm Sci 2014;6(7):9-14.

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 Suppl 1:62-5.

Soares FL, Carneiro RL. Green synthesis of ibuprofen-nicotinamide cocrystals and in-line evaluation by Raman spectroscopy. Cryst Growth Des 2013;13(4):1510-7.

Shayanfar A, Velaga S, Jouyban A. Solubility of carbamazepine, nicotinamide, and carbamazepine-nicotinamide cocrystal in ethanol-water mixtures. Fluid Phase Equilib 2014;363:97-105.

Rager T, Hilfiker R. Application of phase diagrams in co-crystal search and preparation. In: Johan W, Luc Q, editors. Pharmaceutical Salts and Co-Crystals. 1st ed. Cambridge: The Royal Society of Chemistry; 2012. p. 110-27.

Holan J, Stepánek F, Billot P, Ridvan L. The construction, prediction and measurement of co-crystal ternary phase diagrams as a tool for solvent selection. Eur J Pharm Sci 2014;63:124-31.

Grodowska K, Parczewski A. Organic solvents in the pharmaceutical industry. Acta Pol Pharm 2010;67(1):3-12.

The United States Pharmacopoeial Convention, Inc. USP 30 NF 25. Vol. 1. Twinbrook Parkway: The United States Pharmacopoeial Convention, Inc.; 2007.

Yamashita H, Hirakura Y, Yuda M, Teramura T, Terada K. Detection of cocrystal formation based on binary phase diagrams using thermal analysis. Pharm Res 2012;30(1):1-11.

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.

Alatas F, Soewandhi SN, Sasongko L, Ismunandar, Uekusa H. Cocrystal formation between didanosine and two aromatic acids. Int J Pharm Pharm Sci 2013;5 Suppl 3:275-80.

Gerakines PA, Schutte WA, Greenberg JM, van Dishoeck EF. The infrared band strengths of H2O, CO, and CO2 in laboratory simulaions of astrophysical ice mixtures. Astron Astrophys 1995;296:1-17.



How to Cite

Nawatila, R., A. N. W, S. Siswodihardjo, and D. Setyawan. “PREPARATION OF ACYCLOVIR-NICOTINAMIDE COCRYSTAL BY SOLVENT EVAPORATION TECHNIQUE WITH VARIATION OF SOLVENT”. Asian Journal of Pharmaceutical and Clinical Research, vol. 10, no. 3, Mar. 2017, pp. 283-7, doi:10.22159/ajpcr.2017.v10i3.16149.



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