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Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile

Authors Khan FM, Ahmad M, Idrees HA

Received 4 July 2020

Accepted for publication 25 September 2020

Published 19 October 2020 Volume 2020:14 Pages 4303—4313

DOI https://doi.org/10.2147/DDDT.S270742

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos


Fahad Mehmood Khan,1 Mahmood Ahmad,2 Hafiz Arfat Idrees1

1Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab 63100, Pakistan; 2Faculty of Pharmacy, University of Central Punjab, Punjab 54000, Pakistan

Correspondence: Mahmood Ahmad Tel +92 300 9682258
Email ma786_786@yahoo.com

Purpose: To enhance the solubility and dissolution profile of simvastatin (SIM) through co-crystallization with varying ratios of nicotinamide (NIC) using various co-methods.
Materials and Methods: Twelve SIM:NIC co-crystal formulations (F01–F12) were prepared using dry grinding, slurry, liquid-assisted grinding, and solvent-evaporation methods, and their properties compared. Optimized formulations were selected on the basis of dissolution profiles and solubility for in vivo studies. The angle of repose, Carr Index and Hausner ratio were calculated to evaluate flow properties. Differential light scattering (DLS) was used to estimate particle-size distribution. Scanning electron microscopy (SEM) was employed to evaluate surface morphology. Thermal analyses and Fourier-transform infrared (FTIR) spectroscopy were used to determine the ranges of thermal stability and physical interaction of formulated co-crystals. X-ray powder diffraction (XPD) spectroscopy was used to determine the crystalline nature. Solubility and dissolution studies were undertaken to determine in vitro drug-release behaviors.
Results: Micromeritic analyses revealed the good flow properties of formulated co-crystals. DLS showed the particle size of co-crystals to be in the nanometer range. SEM revealed that the co-crystals were regular cubes. Thermal studies showed the stability of co-crystals at > 300°C. FTIR spectroscopy revealed minor shifts of various peaks. XPD spectroscopy demonstrated co-crystal formation. The formulations exhibited an improved dissolution profile with marked improvements in solubility. In vivo studies showed a 2.4-fold increase in Cmax whereas total AUC(0–∞) was increased 4.75-fold as compared with that of SIM tablets.
Conclusion: Co-crystallization with NIC improved the solubility and dissolution profile and, hence, the bioavailability of the poorly water-soluble drug SIM.

Keywords: pharmacokinetics, solubility enhancement, simvastatin, nicotinamide, co-crystal

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