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 o 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. Keywords : Simvastatin, Co-crystal, Nicotinamide, Solubility, Dissolution
Highlights
The effectiveness of drug delivery to a target organ or system in the body depends on the capability to produce suitable formulation of the drug
The bioavailability of an oral preparation depends on its solubility which determines how quickly it is absorbed in the gastrointestinal tract and its permeability over cell membranes [1]
SV is an inhibitor of A (HMG-CoA) reductase; it belongs to the class of statins
Summary
The effectiveness of drug delivery to a target organ or system in the body depends on the capability to produce suitable formulation of the drug. Several methods have been developed to improve the solubility of SV, such as solid dispersion [5], reduction of particle size micro emulsion [6], addition of a surfactant [7], but these methods have been somewhat insufficient They have some shortcomings including, the high energy required of the process. We developed a simple technique of co-crystallization to improve the solubility and dissolution profile of SV using Nic as coformer. Dried co-crystal equivalently to SV 100 mg of reconstituted with 50 mL of distilled water in a vial It was shaken for 24 h using an agitator shaker, the concentration of dissolved SV was determined using validated Uv-Vis spectrophotometry (Analytical Zena, Germany). Profile of co-crystal stability SV: Nic (1:1) was examined thru observing a melting point of the co-crystal that were kept in a storage condition 40 oC and RH 75 % for one month
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