Preparation and physicochemical and preclinical evaluations of recrystallized celecoxib.
The aim of the present study is to increase the aqueous solubility of celecoxib by recrystallization from distilled water, Tween-80, and polyethylene glycol-400. The prepared crystals were evaluated for various physicochemical evaluations, dissolution rate, and in vivo performance like analgesic activity (by writhing and hot plate method) and pharmacokinetics in mice. The practical yield of the crystals ranged between 83 and 98%, and celecoxib content was more than 99%. Celecoxib showed an almost 5-fold increase in solubility when recrystallized in the presence of Tween-80 (2%). The dissolution rates of celecoxib from the co-crystal forms were considerably higher than that of plain celecoxib. The infrared and differential scanning calorimetry studies indicated the absence of a well-defined interaction between celecoxib and carriers. The differential scanning calorimetry and X-ray diffraction studies indicated the amorphization or partial amorphization of the drug. The scanning electron microscopy showed fluffy, porous, and fine particles in recrystallized celecoxib. The particle size of prepared co-crystals was considerably reduced in comparison with plain celecoxib. The crystals prepared with Tween-80 (2%) showed significantly higher analgesic activity than plain celecoxib. In pharmacokinetic study, the prepared crystals exhibited significantly high and rapid absorption along with improved bioavailability.
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India. ssmutalik@yahoo.com
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Mutalik
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Usha
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Ranjith
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Umesh
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Musmade
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Anup
D019342:Acetic Acid; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006358:Hot Temperature; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010146:Pain / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013449:Sulfonamides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011136:Polysorbates; D011720:Pyrazoles; D012997:Solvents; D013449:Sulfonamides; D011092:Polyethylene Glycols; D000068579:Celecoxib; D019342:Acetic Acid