Development and evaluation of a gastroretentive drug delivery system for the low-absorption-window drug celecoxib.
The objective of the present study is to develop microspheres for celecoxib to enhance its bioavailability by increasing its gastric residence time. Four different polymers-polyethylene oxide, Eudragit S, cellulose acetate, and Eudragit RL-were used to form the floating microspheres using an emulsion-solvent diffusion technique. The use of two different solvents (dichloromethane and ethanol) that differed in the rate of diffusion led to formation of a hollow core in the microspheres, which was partially responsible for the flotation ability. The formulation was optimized on the basis of in vitro buoyancy and in vitro release in simulated gastric fluid at pH 3. Scanning electron microscopy revealed differences between the formulations in terms of their topography. X-ray diffractometry and differential scanning calorimetry examination showed the amorphous nature of the drug. Microspheres prepared with polyethylene oxide:Eudragit S:celecoxib (2:2:1) gave the best in vitro percentage release and was taken as the optimized formulation. By fitting the data into zero order, first order, and Higuchi model, it could be concluded that the release followed first-order release kinetics. The correlation coefficient (R2 value) was obtained upon fitting the data to Higuchi equation, which signifies that the mechanism of release of celecoxib from the microspheres was diffusion rate-limited.
Ali
Javed
J
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India. javedaali@yahoo.com
Tyagi
Puneet
P
Ahuja
Alka
A
Baboota
Sanjula
S
Hasan
Sohail
S
D000068579:Celecoxib; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008752:Methylene Chloride / Q000737:chemistry; D008863:Microspheres; D008956:Models, Chemical; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D016062:Porosity; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods
D016861:Cyclooxygenase Inhibitors; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D011109:Polymethacrylic Acids; D011720:Pyrazoles; D012997:Solvents; D013449:Sulfonamides; C038300:methylmethacrylate-methacrylic acid copolymer; C005062:acetylcellulose; D000431:Ethanol; D011092:Polyethylene Glycols; C058665:Eudragit RL; D008752:Methylene Chloride; D002482:Cellulose; D000068579:Celecoxib