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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-5996
Vol. 16, No. 2, 2017, pp. 297-303
Bioline Code: pr17039
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 16, No. 2, 2017, pp. 297-303

 en Simvastatin-nicotinamide co-crystal: design, preparation and preliminary characterization
Sopyan, Iyan; Fudholi, Achmad; Muchtaridi, Muchtaridi & Sari, Ika Puspita


Purpose: To improve the solubility of simvastatin (SV) by co-crystallization using nicotinamide (Nic) as co-crystal agent (co-former).
Methods: In silico molecular modeling of Nic counter to SV were investigated using Auto Dock 4.2. Co-crystal of Nic-SV was obtained by solvent evaporation (SE) using an equimolar ratio of Nic and SV. Co-crystal of SV-Nic was evaluated by scanning electron microscopy (SEM), saturated solubility, intrinsic dissolution, x-ray powder diffraction (XRPD), differential scanning calorimetric (DSC), infrared spectrophotometry (FT-IR), binary phase diagram, and for stability at 40 oC and relative humidity (RH) 75% in one month.
Results: In silico results showed that the interaction of Nic with SV took place through hydrogen bonding as the synthon agent. The solubility and intrinsic dissolution properties of the co-crystal improved significantly compared to pure SV. Characterization of the co-crystal SV: Nic (1: 1) by SEM, XRPD, DSC, FT-IR, and binary phase diagram indicate the formation of a new solid phase that was different from either SV or Nic. Furthermore, the cocrystal of SV: Nic remained stable for one month.
Conclusion: Co-crystallization using Nic has the potential to enhance drug solubility, intrinsic dissolution, and the stability of solution.

Simvastatin; Co-crystal; Nicotinamide; Solubility; Dissolution

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