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.
Highlights
Meloxicam (molecular structure shown in Figure 1, IUPAC name: 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H1,2-benzothiazine-3-carboxamide-1,1-dioxide, molar mass 351.40 g·mol–1, CAS number: 71125-38-7, PubChem CID: 54677470) is a non-steroidal anti-inflammatory drug commonly employed in current therapeutics for pain and inflammatory treatments.[1,2,3,4,5] Meloxicam exhibits a very low solubility in pure water, which influences in vitro and in vivo dissolution rates, affecting negatively its biological activity
Because the very low equilibrium solubility of meloxicam in neat water, this property has been studied in {2-propanol + water} mixtures from (293.15 to 313.15) K to expand the solubility database of pharmaceuticals in mixed solvents useful for liquid dosage forms design
Meloxicam solubility increases with temperature arising and maximum value is observed in the mixture x1 = 0.70 at all temperatures
Summary
Meloxicam (molecular structure shown in Figure 1, IUPAC name: 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H1,2-benzothiazine-3-carboxamide-1,1-dioxide, molar mass 351.40 g·mol–1, CAS number: 71125-38-7, PubChem CID: 54677470) is a non-steroidal anti-inflammatory drug commonly employed in current therapeutics for pain and inflammatory treatments.[1,2,3,4,5] Meloxicam exhibits a very low solubility in pure water, which influences in vitro and in vivo dissolution rates, affecting negatively its biological activity. GC - Solubility of Meloxicam in Aqueous Mixtures of 2-Propanol procedure mentioned above to determine meloxicam concentrations All these procedures were performed successively until solid-liquid equilibrium was achieved at 293.15 K. X-Ray Diffraction (XRD) analysis To determine the crystal nature of the solid meloxicam samples, both before and after the saturation in neat water, in the mixture of x1 = 0.50, and in neat 2-propanol, the respective X-ray powder diffraction analyses were performed by using a PANalytical Xpert Pro X-ray diffractometer. Fourier Transform Infrared (FTIR) analysis to XRD analyses, in order to confirm the nature of the solid meloxicam samples, both before and after the saturation in neat water, in the mixture of x1 = 0.50, and in neat 2-propanol, FTIR analyses were performed. The respective spectra were obtained in a FTIR spectrophotometer (IRAffinity-1, Shimadzu, Japan)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
