Simvastatin-nicotinamide co-crystal: design, preparation and preliminary characterization
Abstract
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 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.
Keywords: Simvastatin, Co-crystal, Nicotinamide, Solubility, Dissolution
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.
