期刊
TROPICAL JOURNAL OF PHARMACEUTICAL RESEARCH
卷 16, 期 2, 页码 297-303出版社
PHARMACOTHERAPY GROUP
DOI: 10.4314/tjpr.v16i2.6
关键词
Simvastatin; Co-crystal; Nicotinamide; Solubility; Dissolution
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. Cocrystal of Nic-SV was obtained by solvent evaporation (SE) using an equimolar ratio of Nic and SV. Cocrystal 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 degrees C 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.
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