Co-crystallization: A Tool to Enhance Solubility and Dissolution Rate of Simvastatin

    Published on:April 2017
    Journal of Young Pharmacists, 2017; 9(2):183-186
    Original Article | doi:10.5530/jyp.2017.9.36

    Iyan Sopyan1,2, Achmad Fudholi1*, Muchtaridi Muchtaridi3, Ika Puspita Sari4

    1Department of Pharmaceutical and Technology Formulation of University of Gadjah Mada, Yogyakarta, 55281, INDONESIA.

    2Department of Pharmaceutical and Technology Formulation of University of Padjadjaran, Bandung, INDONESIA.

    3Department of Pharmaceutical Analysis and Medicinal Chemistry, Pharmacy Faculty, University of Padjadjaran, Bandung, INDONESIA.

    4Department of Pharmacology and Clinical Pharmacy, Faculty Pharmacy, University of Gadjah Mada, Yogyakarta, 55281, INDONESIA..


    Objective : The aim of this study was to explore co-crystallization to enhance the solubility of simvastatin (SV) as a drug of choice for hypercholesterolemia using saccharin (Sacch) as co-former. Methods: Molecular modeling of sacch against SV has been conducted by in silico using auto dock 4.2. Preparation of co-crystal has carried out by solvent evaporation (SE) using an equimolar ratio of SV and Sacch. Co-crystal of SV- Sacch was evaluated by the saturated solubility test and intrinsic dissolution test. Afterward, the co-crystal was characterized by infrared spectrophotometry (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), binary phase diagram and stability studies in storage condition 400C and relative humidity (RH) 75% for three months. Results: In silico studies showed that the interaction of SV against sacch has hydrogen bonding as molecular synthon. Evaluations of solubility and intrinsic dissolution have shown an increased in rate properties significantly of co-crystal as compared to pure SV and its physical mixer (PM). Characterizations of a co-crystal SV: sacch (1: 1) has indicated the formation of different new solid crystal phase as compared to SV, sacch, and its PM, and stable for 400C and RH 75% in 3 months. Conclusion: Co-crystallization has been used to increase the solubility and dissolution rate of simvastatin and all characterization has shown the formation of co-crystal SV: sacch (1: 1).

    Key words: Co-crystal, Simvastatin, Saccharin, Solubility, Dissolution.

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