Solubilization and thermodynamic properties of simvastatin in various micellar solutions of different non-ionic surfactants: Computational modeling and solubilization capacity

Faiyaz Shakeel,Ehab M Elzayat,Nazrul Haq,Mohammad Altamimi,Sultan Alshehri,Mohamed A Ibrahim,Gamal A Shazly,Mª Ángeles Peña Fernández

doi:10.1371/journal.pone.0249485

Faiyaz Shakeel, Ehab M Elzayat + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0249485

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Journal: PLOS ONE	Publication Date: Apr 8, 2021
Citations: 11	License type: CC BY 4.0

Affiliation: King Saud University, Al Azhar University

Abstract

The aim of this work was to solubilize simvastatin (SIM) using different micellar solutions of various non-ionic surfactants such as Tween-80 (T80), Tween-20 (T20), Myrj-52 (M52), Myrj-59 (M59), Brij-35 (B35) and Brij-58 (B58). The solubility of SIM in water (H2O) and different micellar concentrations of T80, T20, M52, M59, B35 and B58 was determined at temperatures T = 300.2 K to 320.2 K under atmospheric pressure p = 0.1 MPa using saturation shake flask method. The experimental solubility data of SIM was regressed using van’t Hoff and Apelblat models. The solubility of SIM (mole fraction) was recorded highest in M59 (1.54 x 10−2) followed by M52 (6.56 x 10−3), B58 (5.52 x 10−3), B35 (3.97 x 10−3), T80 (1.68 x 10−3), T20 (1.16 x 10−3) [the concentration of surfactants was 20 mM in H2O in all cases] and H2O (1.94 x 10−6) at T = 320.2 K. The same results were also recorded at each temperature and each micellar concentration of T80, T20, M52, M59, B35 and B58. “Apparent thermodynamic analysis” showed endothermic and entropy-driven dissolution/solubilization of SIM in H2O and various micellar solutions of T80, T20, M52, M59, B35 and B58.

Highlights

Simvastatin (SIM) {molecular structure: Fig 1; chemical name: [(1S,3R,7S,8S,8aR)-8-[2[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen1-yl] 2,2-dimethylbutanoate; molecular formula: C25H38O5; molar mass: 418.57 g mol-1 and CASRN: 79902-63-9) occurs as a white to off-white crystalline powder [1, 2]
The solid phases of SIM in both samples were characterized for the investigation their physical form and possible transformation of SIM into polymorphs/solvates/hydrates after equilibrium
differential scanning calorimetry (DSC) thermograms of SIM in pure and equilibrated samples are shown in Fig 2A and 2B, respectively

Summary

Introduction

Simvastatin (SIM) {molecular structure: Fig 1; chemical name: [(1S,3R,7S,8S,8aR)-8-[2[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen1-yl] 2,2-dimethylbutanoate; molecular formula: C25H38O5; molar mass: 418.57 g mol-1 and CASRN: 79902-63-9) occurs as a white to off-white crystalline powder [1, 2]. It is a lipid lowering agent which belongs to statins family and powerful inhibitor of (3,5)-hydroxy-3-methylglutaryl coenzyme A (HMGr-CoA) reductase [3, 4]. It shows very poor bioavailability (< 5.0%) upon oral administration which may be attributed to its poor solubility in water, low intestinal uptake and extensive first pass metabolism [2, 8, 9].

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