Multicomponent crystals increase simvastatin solubility

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1079-1089, Nov-Dec 2024. DOI: https://doi.org/10.56499/jppres23.1898_12.6.1079 Original Article Multicomponent crystals: Solubility enhancement of simvastatin using arginine and glycine coformers [Cristales multicomponentes: Mejora de la solubilidad de la simvastatina utilizando coformadores de arginina y glicina] Iyan Sopyan1,2*, Karyn Elizabeth1, Sandra Megantara3, Silmy Kaffah1 1Department of Pharmaceutics and Pharmaceutical … Continue reading Multicomponent crystals increase simvastatin solubility

J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1079-1089, Nov-Dec 2024.

DOI: https://doi.org/10.56499/jppres23.1898_12.6.1079

Original Article

Multicomponent crystals: Solubility enhancement of simvastatin using arginine and glycine coformers

[Cristales multicomponentes: Mejora de la solubilidad de la simvastatina utilizando coformadores de arginina y glicina]

Iyan Sopyan1,2*, Karyn Elizabeth1, Sandra Megantara3, Silmy Kaffah1

1Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, 45363, Indonesia.

2Study Center of Drugs Dosage Form Development, Faculty of Pharmacy, Padjadjaran University, Sumedang, West Java, 45363, Indonesia.

3Department Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, 45363, Indonesia.

*E-mail: i.sopyan@unpad.ac.id

Abstract

Context: Simvastatin can be modified by the formation of multicomponent crystals to increase its solubility.

Aims: To compare the solubility of multicomponent simvastatin crystals to pure simvastatin.

Methods: The in silico study of simvastatin and the coformers arginine and glycine revealed non-covalent interactions, so multicomponent preparations of simvastatin crystals were prepared by solvent evaporation using a mole ratio of 1:1; 1:2 and 2:1.

Results: Each simvastatin-arginine and simvastatin-glycine ratio increased the solubility, with the highest increase observed for the 1:2 ratio compared to pure simvastatin.

Conclusions: Simvastatin-arginine multicomponent crystals (1:2) showed the best dissolution profile in phosphate buffer medium pH 7.0 with 67.69% dissolution, while simvastatin-glycine multicomponent crystals (1:2) exhibited the best dissolution profile in buffer media pH 1.2 with 16.19% dissolution. Characterization of the multicomponent crystals revealed a shift in the peaks, a decreased melting point, and enthalpy, indicating decreased % crystallinity and the formation of a new solid phase.

Keywords: arginine; glycine; multicomponent crystal; simvastatin; solubility enhancement.

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Resumen

Contexto: La simvastatina puede modificarse mediante la formación de cristales multicomponentes para aumentar su solubilidad.

Objetivos: Comparar la solubilidad de cristales multicomponentes de simvastatina con la simvastatina pura.

Métodos: El estudio in silico de la simvastatina y los coformadores arginina y glicina reveló interacciones no covalentes por lo que se prepararon preparaciones multicomponente de cristales de simvastatina por evaporación de disolvente utilizando una proporción molar de 1:1; 1:2 y 2:1.

Resultados: Cada relación simvastatina-arginina y simvastatina-glicina aumentó la solubilidad, observándose el mayor aumento para la relación 1:2 en comparación con la simvastatina pura.

Conclusiones: Los cristales multicomponentes de simvastatina-arginina (1:2) mostraron el mejor perfil de disolución en medio tampón fosfato pH 7,0 con un 67,69% de disolución, mientras que los cristales multicomponentes de simvastatina-glicina (1:2) exhibieron el mejor perfil de disolución en medio tampón pH 1,2 con un 16,19% de disolución. La caracterización de los cristales multicomponente reveló un desplazamiento de los picos, una disminución del punto de fusión y de la entalpía, lo que indica una disminución del % de cristalinidad y la formación de una nueva fase sólida.

Palabras Clave: arginina; cristal multicomponente; glicina; mejora de la solubilidad; simvastatina.

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Citation Format: Sopyan I, Megantara S, Elizabeth K, Kaffah S (2024) Multicomponent crystals: Solubility enhancement of simvastatin using arginine and glycine coformers. J Pharm Pharmacogn Res 12(6): 1079–1089. https://doi.org/10.56499/jppres23.1898_12.6.1079
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