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Pharm Sci. 2022;28(1): 130-144.
doi: 10.34172/PS.2021.39

Scopus ID: 85124288756
  Abstract View: 422
  PDF Download: 446

Research Article

Solubility, Correlation, Dissolution Thermodynamics and Preferential Solvation of Meloxicam in Aqueous Mixtures of 2-Propanol

Darío A Tinjacá 1 ORCID logo, Fleming Martinez 1* ORCID logo, Ovidio A Almanza 2 ORCID logo, Abolghasem Jouyban 3,4 ORCID logo, William E Acree 5 ORCID logo

1 Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Departamento de Farmacia, Grupo de Investigaciones Farmacéutico-Fisicoquímicas, Cra. 30 No. 45-03, Bogotá D.C., Colombia.
2 Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Departamento de Física, Grupo de Física Aplicada, Cra. 30 No. 45-03, Bogotá D.C., Colombia.
3 Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Immunology Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Department of Chemistry, University of North Texas, Denton, TX 76203-5070, USA.
*Corresponding Author: Email: fmartinezr@unal.edu.co

Abstract

Background: Meloxicam is a powerful analgesic and anti-inflammatory drug widely prescribed by physicians in current therapeutics. Because of the very low aqueous equilibrium solubility of meloxicam, this property has been studied in {2-propanol + water} mixtures from (293.15 to 313.15) K to expand the solubility database about pharmaceutical compounds in mixed solvents useful for homogeneous liquid dosage forms design.

Methods: Flask shaken method and UV-vis spectrophotometry were used for meloxicam solubility determinations. Jouyban-Acree model was challenged for solubility correlation. The van’t Hoff and Gibbs equations were employed here to calculate the respective apparent standard thermodynamic quantities for the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy. In addition, the inverse Kirkwood-Buff integrals were employed to compute the preferential solvation parameters of meloxicam by 2-propanol in the mixtures.

Results: Meloxicam solubility increases with temperature arising and maximum solubilities are observed in the mixture of x1 = 0.70 at all temperatures. Jouyban-Acree model correlates the meloxicam solubility very well. Dissolution processes were endothermic in all cases and entropy-driven in the interval 0.20 ≤ x1 ≤ 1.00. Non-linear enthalpy–entropy relationship was observed in the plot of enthalpy vs. Gibbs energy exhibiting negative but variant slopes in the composition region 0.00 < x1 < 0.40 and variant negative and positive slopes in the other mixtures. Meloxicam is preferentially solvated by water in water-rich mixtures, it is apparently solvated by water in 2-propanol-rich mixtures, but it is preferentially solvated by 2-propanol in the composition interval of 0.19 < x1 < 0.78.

Conclusion: Solid-liquid equilibrium of meloxicam in {2-propanol + water} mixtures has been studied at several temperatures as a contribution to preformulation studies of homogeneous liquid pharmaceutical dosage forms based on this drug.

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Submitted: 18 May 2021
Revision: 27 Jun 2021
Accepted: 04 Jul 2021
ePublished: 11 Jul 2021
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