Drug Design, Development and Therapy (Mar 2016)

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

  • Meor Mohd Affandi MMR,
  • Tripathy M,
  • Shah SAA,
  • Majeed ABA

Journal volume & issue
Vol. 2016, no. Issue 1
pp. 959 – 969

Abstract

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MMR Meor Mohd Affandi,1,2 Minaketan Tripathy,1,3 Syed Adnan Ali Shah,3,4 ABA Majeed1,3 1Laboratory of Fundamental Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, Selangor, Malaysia; 2DDH Core, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor Darul Ehsan, Malaysia; 3Pharmaceutical and Life Sciences Core, Universiti Teknologi MARA (UiTM), Shah Alam, Selangor Darul Ehsan, Malaysia; 4Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, Selangor, Malaysia 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. Keywords: simvastatin–arginine complex, solubility, volumetric, conductometric, spectroscopy

Keywords