Multivesicular liposomes bearing celecoxib-beta-cyclodextrin complex for transdermal delivery.
In our work depot delivery systems of celecoxib were developed using multivesicular liposomes. Moreover, the solubility of celecoxib was enhanced by complexing drug with cyclodextrin to overcome the limitation of conventional therapy. The multivesicular liposomes (MVLs) bearing celecoxib-beta -cyclodextrin inclusion complex were prepared by reverse phase evaporation method, and multilamellar vesicles (MLVs)-bearing drug complex was prepared by the cast film method. The formulations were characterized for vesicle size, encapsulation efficiency, and in vitro drug release. In vivo performance of multivesicular liposomes bearing celecoxib-beta -cyclodextrin inclusion complex was evaluated by assessing anti-inflammatory activity using carrageenan-induced rat paw edema volume method. The results were compared with that of celecoxib-cyclodextrin complex and MLVs containing celecoxib-beta -cyclodextrin inclusion complex in equal amounts. Phase solubility studies for the celecoxib-beta -cyclodextrin inclusion complex clearly indicated an increase in aqueous solubility of celecoxib with an increase in beta -CD concentration. The in vitro release studies reveal that MLVs release more than 80% drug within 48 hr whereas MVL formulations release nearly the same amount of drug in 120 hr. In vivo data reveal that reduction in paw volume with MVL formulation was not rapid and fast, but the effect was maintained for prolonged periods, and even after 24 hr there was 40.7 +/- 3.40% reduction in paw volume. MVL formulation showed more sustained and prolonged anti-inflammatory effect compared with plain drug and MLVs. We concluded that multivesicular liposome can be successfully utilized for the sustained delivery of celecoxib.
Jain
Sanjay K
SK
Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, India. drskjainsagar@rediffmail.com
Gupta
Yashwant
Y
Jain
Anekant
A
Bhola
Megha
M
D000279:Administration, Cutaneous; D000818:Animals; D002351:Carrageenan; D000068579:Celecoxib; D002626:Chemistry, Pharmaceutical; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D010316:Particle Size; D010539:Permeability; D011720:Pyrazoles / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D012869:Skin Absorption; D012995:Solubility; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics
D052246:Cyclooxygenase 2 Inhibitors; D003692:Delayed-Action Preparations; D008081:Liposomes; D011720:Pyrazoles; D013449:Sulfonamides; D047392:beta-Cyclodextrins; D002351:Carrageenan; D000068579:Celecoxib; C031215:betadex