Solubility enhancement of Cox-2 inhibitors using various solvent systems.
This study examined the solubility enhancement of 4 cox-2 inhibitors, celecoxib, rofecoxib, meloxicam, and nimesulide, using a series of pure solvents and solvent mixtures. Water, alcohols, glycols, glycerol, and polyethylene glycol 400 (PEG 400) were used as solvents and water-ethanol, glycerol-ethanol, and polyethylene glycol-ethanol were used as mixed-solvent systems. A pH-solubility profile of drugs was obtained in the pH range 7.0 to 10.9 using 0.05 M glycine-sodium hydroxide buffer solutions. Lower alcohols, higher glycols, and PEG 400 were found to be good solvents for these drugs. The aqueous solubility of celecoxib, rofecoxib, and nimesulide could be enhanced significantly by using ethanol as the second solvent. Among the mixed-solvent systems, PEG 400- ethanol system had highest solubilization potential. In the case of meloxicam and nimesulide, solubility increased significantly with increase in pH value. Physico-chemical properties of the solvent such as polarity, intermolecular interactions, and the ability of the solvent to form a hydrogen bond with the drug molecules were found to be the major factors involved in the dissolution of drugs by pure solvents. The greater the difference in the polarity of the 2 solvents in a given mixed solvent, the greater was the solubilization power. However, in a given mixed-solvent system, the solubilization power could not be related to the polarity of the drugs. Significance of the solubility data in relation to the development of formulations has also been discussed in this study.
Seedher
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Department of Chemistry, Panjab University, Chandigarh-160014, India. nseedher@yahoo.com
Bhatia
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D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical / Q000379:methods; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry; D000077239:Meloxicam; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry*; D011720:Pyrazoles; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry; D013450:Sulfones; D013843:Thiazines / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007783:Lactones; D011720:Pyrazoles; D012997:Solvents; D013449:Sulfonamides; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; C116926:rofecoxib; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; C012655:nimesulide; D000077239:Meloxicam