COCRYSTALLIZATION ACYCLOVIR-SUCCINIC ACID USING SOLVENT EVAPORATION METHODS


Agnes Nuniek Winantari, Dwi Setyawan, Siswandono Siswodihardjo, Sundono Nurono Soewandhi

Abstract


Objective : The aim of this research is to prepare and characterize cocrystals of acyclovir through cocrystallization of acyclovir – succinic acid (AS) to improve the physical properties of the drug.  

Methods : AS cocrystals was prepared using solvent evaporation method. The cocrystals were  characterized by Polarization Microscope, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC),  Powder X-Ray Diffraction (PXRD), and Fourier Transform Infrared Spectroscopy (FTIR).

Results : Physical characterization using polarization microscope and SEM showed the AS cocrystals have unique crystal habit and morphology. Phase diagram at molar ratio of 50% : 50% (acyclovir : succinic acid) showed a decrease in the melting temperature i.e 176.23 oC  in comparison with the melting point of the constituent  materials (acyclovir 253.53 oC and succinic acid 187.29 oC).  The PXRD pattern of AS cocrystals (ethanol) exhibited new diffraction peaks at 2θ = 5.91; 9.16; and 13.40. Besides, cocrystals of AS (glacial acetic acid) indicated new peaks at  2θ = 5.98; 9.19; and 13.43.  Furthermore, there was a shift in the N-H, O-H and C=O.

Conclusion : Cocrystallization of acyclovir-succinic acid (AS) in ethanol and glacial acetic acid were succesfully formed using solvent evaporation methods.

 

 


Keywords


acyclovir, succinic acid, cocrystal, characterization, solvent evaporation method

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References


Jones W, Motherwell WD, Trask AV. Pharmaceutical co-crystals: An emerging approach to physical property enhancement. MRS Bull 2006;31:875-9.

Shultheiss N, Newman A. Pharmaceutical and their physicochemical properties. Cryst Growth Des 2009;9:2950-67.

Sarma B, Chen J, Hsi H, Myerson AS. Solid forms of pharmaceuticals: Polymorphs, salts and co-crystals. Korean J Chem Eng 2011;28(2):315-22.

Sekhon BS. Pharmaceutical co-crystals - An update. Int Bull Drug Res 2012;1(2):24-39.

Mingyu L, Hong BC, Yao Y, Shen H, Ji G, Li G, et al. Development of a pharmaceutical co-crystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals. Eur J Pharm Biopharm 2016;107:151-9.

Sevukarajan M, Thanuja B, Riyaz S, Rahul N. Synthesis and characterization of a pharmaceutical co-crystal (Aceclofenac: Nicotinamide). J Pharm Sci Res 2011;3(6):1288-93.

Nanjwade VK, Manvi FV, Shamrez AM, Basavaraj KN, Meenaxi MM. New trends in the co-crystallization of active pharmaceutical ingredients. J Appl Pharm Sci 2011;1(8):1-5.

Santos OM, Reis ME, Jacon JT, Lino ME, Simoes JS, Doriguetto AC. Polimorphism: An evaluation of the potential risk to the quality of drug products from the farmacia popular rede propria. Braz J Pharm Sci 2014;50(1):1-24.

Almarsson O, Zaworotko MJ. Crystal engineering of the composition of pharmaceutical phases. Do pharmaceutical co-crystals represent a new path to improved medicines? Chem Commun 2004;35(6):1889-96.

Najar AA, Azim Y. Pharmaceutical co-crystals: A new paradigm of crystal engineering. J Indian Inst Sci 2014;94(1):45-67.

Masuda T, Yoshihashi Y, Yonemochi E, Fujii K, Uekusa H. Co-crystallization and amorphization induced by drug-excipient interaction improves the physical properties of acyclovir. Int J Pharm 2012;422:160-9.

Bruni G, Maietta M, Maggi L, Mustarelli P, Ferrara C, Berbenni V, et al. Preparation and physicochemical characterization of acyclovir co-crystals with improved dissolution properties. J Pharm Sci 2013;102(11):4079-86.

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

Sarkar A, Rohani S. Co-crystal of acyclovir with promising physicochemical properties. J Pharm Sci 2015;104:98-105.

Munde AV, Kumar FN, Radheshyam BK. Co-crystallization: An alternative approach for solid modification. J Drug Ther 2013;3(4):166-72.

Partogi T, Soewandhi SN, Pamudji JS, Wikarsa S. Identification of physical interaction between anti malarial drugs combination artesunate-amodiaquine hydrochloride. Int J Pharm Pharm Sci 2013;5(3):206-10.

Setyawan D, Sari R, Yusuf H, Primaharinastiti R. Preparation and characterization of artesunate-nicotinamide co-crystal by solvent evaporation and slurry method. Asian J Pharm Clin Res 2014;7(1):62-5.

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

Reutzel-Edens SM. Analytical techniques and strategies for salt, co-crystal characterization. In: Wouters J, Luc Q, editors. Pharmaceutical Salts and Co-crystals. RSC Drug Discovery Series No. 16. Cambridge: Royal Society of Chemistry Publishing; 2012. p. 220.

Allam AN, Naggar VF, El Gamal SS. Formulation and physicochemical characterization of chitosan/acyclovir co-crystals. Pharm Dev Technol 2013;18(4):856-65.

Brittain HG. Polymorphism in Pharmaceutical Solids. New York: Marcel Dekker; 1999.

Barboza F, Vecchia DD, Tagliar MP, Silva MA, Stulzer HK. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations. Pharm Chem J 2009;43:363-8.

Ober CA, Gupta RB. Formation of itraconazole-succinic acid co-crystals by gas antisolvent cocrystallization. AAPS Pharm Sci Technol 2012;13(4):1396-405.




About this article

Title

COCRYSTALLIZATION ACYCLOVIR-SUCCINIC ACID USING SOLVENT EVAPORATION METHODS

Keywords

acyclovir, succinic acid, cocrystal, characterization, solvent evaporation method

DOI

10.22159/ajpcr.2017.v10i6.16369

Date

01-06-2017

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 10 Issue 6 June 2017 Page: 91-94

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

127 Views | 47 Downloads

Authors & Affiliations

Agnes Nuniek Winantari
Department of Pharmaceutics, Faculty of Pharmacy, University of Surabaya, Surabaya, Indonesia.
Indonesia

Dwi Setyawan
Department of Pharmaceutics, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia.
Indonesia

Siswandono Siswodihardjo
Department of Medicinal Chemistry, Faculty of Pharmacy, Airlangga University, Surabaya, Indonesia.
Indonesia

Sundono Nurono Soewandhi
Department of Pharmaceutics, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia
Indonesia


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