Fahad M Khan1,
Mahmood Ahmad2 
,
Fakhra Batool1
For correspondence:- Mahmood Ahmad Email: ma786_786@yahoo.com Tel:+923009682258
Accepted: 16 November 2019 Published: 30 December 2019
Citation: Khan FM, Ahmad M, Batool F. Enhancement of solubility and release profile of simvastatin by co-crystallization with citric acid. Trop J Pharm Res 2019; 18(12):2465-2472 doi: 10.4314/tjpr.v18i12.1
© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Purpose: To enhance the solubility and dissolution profile of simvastatin (SIM) via co-crystallization with varying levels of citric acid using various techniques.
Method: Simvastatin-citric acid (SIM-CA) co-crystals were prepared using dry grinding, slurry, liquid-assisted grinding, and solvent evaporation techniques, and their various properties were compared. A total of twelve formulations (CC01 to CC12) were prepared. Optimized formulations were selected on the basis of dissolution profiles. Flow properties were evaluated using micromeritic analysis, yielding angle of repose, Carr’s index and Hausner’s ratio. Zeta sizer was employed to evaluate particle size distribution, while surface morphology was determined using scanning electron microscopy (SEM). Melting temperature, stability and physical interaction of simvastatin-citric acid co-crystals were determined by thermal analysis and FTIR. The crystalline nature of the co-crystals was evaluated by powder x-ray diffraction analysis, while solubility and dissolution studies were performed to determine in vitro drug release behavior.
Results: Micromeritic analysis revealed good flow properties of SIM-CA co-crystals. Results of Zeta sizer analysis showed that the particle sizes of the co-crystals were in the nanometer range, while SEM revealed that the co-crystals had regular cubical shape. Thermal stability studies with TGA and DSC showed that the co-crystals were stable at temperatures exceeding 400 oC. FTIR results revealed minor shifts in 2956 and 1706 cm-1 peaks. Co-crystal formation was confirmed by PXRD data. The drug release profiles of the optimized formulations (CC02, CC07 and CC11) were 11.36 - 94.46, 12.36 - 95.46 and 13.36 - 96.46 %, respectively. There was significant improvement in solubilities of the optimum formulations, with values of 310.18, 427.21 and 522.02 % for CC02, CC07 and CC11, respectively.
Conclusion: Citric acid improves the solubility and dissolution profile of the poorly water-soluble drug, simvastatin, which suggests that co-crystallization can potentially enhance the bioavailability of the drug.
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