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Original Research

Solubility enhancement of simvastatin by arginine: thermodynamics, solute–solvent interactions, and spectral analysis

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Pages 959-969 | Published online: 02 Mar 2016
 

Abstract

We examined the solubility of simvastatin in water in 0.01 mol·dm−3, 0.02 mol·dm−3, 0.04 mol·dm−3, 0.09 mol·dm−3, 0.18 mol·dm−3, 0.36 mol·dm−3, and 0.73 mol·dm−3 arginine (ARG) solutions. The investigated drug is termed the solute, whereas ARG the cosolute. Phase solubility studies illustrated a higher extent of solubility enhancement for simvastatin. The aforementioned system was subjected to conductometric and volumetric measurements at temperatures (T) of 298.15 K, 303.15 K, 308.15 K, and 313.15 K to illustrate the thermodynamics involved and related solute–solvent interactions. The conductance values were used to evaluate the limiting molar conductance and association constants. Thermodynamic parameters (ΔG0, ΔH0, ΔS0, and Es) for the association process of the solute in the aqueous solutions of ARG were calculated. Limiting partial molar volumes and expansibilities were evaluated from the density values. These values are discussed in terms of the solute–solvent and solute–cosolute interactions. Further, these systems were analyzed using ultraviolet–visible analysis, Fourier-transform infrared spectroscopy, and 13C, 1H, and two-dimensional nuclear overhauser effect spectroscopy nuclear magnetic resonance to complement thermophysical explanation.

Acknowledgments

The authors are thankful to Hovid Berhad for providing SMV powder and the Faculty of Pharmacy (UiTM) for support and cooperation in the completion of this study. This study was supported by Long Term Grant Scheme (600-RMI/LRGS 5/3 (3/2012), Ministry of Higher Education, Government of Malaysia, and Research Excellence Fund (600-RMI/DANA 5/3/REI (3/2013), Research Management Centre (RMC), Universiti Teknologi MARA, Malaysia.

Disclosure

The authors report no conflicts of interest in this work.