Formulation and ex vivo evaluation of rofecoxib gel for topical application.
The potential gastrointestinal disorders associated with oral administration of rofecoxib can be avoided by delivering the drug to the inflammation site at a sustained, concentrated level over an extended period of time. Hydroxypropylmethylcellulose (HPMC), sodium alginate and Carbopol 940 were used in an attempt to develop topical gel formulations of rofecoxib. The effects of polymer composition on the rate of drug release from the gel formulations were examined through cellulose membrane mounting on a Keshary-Chien diffusion cell. The effects of initial drug concentration and viscosity on the permeation rate of rofecoxib from the gel formulations were evaluated using rat epidermis at 37 +/- 0.5 degrees C. The anti-inflammatory activity of the rofecoxib gel formulation was evaluated using the rat hind paw edema model. The gel formulation consisting of 4% w/w sodium alginate-Carbopol 940 at 3:1 ratio was found to be suitable for topical application based on in vitro evaluation and ex vivo permeation studies. The drug permeation rate increased with an increase of the initial drug concentration in gels up to 25% w/w. An inverse relationship was observed between the in vitro drug release rate/ex vivo permeation rate and viscosity of the gel formulations. The anti-inflammatory activity of 4% w/w sodium alginate-Carbopol 940 gel containing 25% w/w rofecoxib in the rat hind paw edema model reveals that the drug was delivered to the inflammation site at a controlled level over a period of 6 h. These results suggest the feasibility of the topical gel formulation of rofecoxib.
Das
Malay K
MK
Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh 786004, India. du_mkd@yahoo.co.in
Ahmed
Abdul B
AB
D000180:Acrylic Resins / Q000008:administration & dosage; D000279:Administration, Cutaneous; D000464:Alginates / Q000008:administration & dosage; D000818:Animals; D002626:Chemistry, Pharmaceutical; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D005782:Gels; D020723:Glucuronic Acid / Q000008:administration & dosage; D006603:Hexuronic Acids / Q000008:administration & dosage; D065347:Hypromellose Derivatives; D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D013450:Sulfones / Q000008:administration & dosage* / Q000737:chemistry; D014783:Viscosity
D000180:Acrylic Resins; D000464:Alginates; D052246:Cyclooxygenase 2 Inhibitors; D003692:Delayed-Action Preparations; D005782:Gels; D006603:Hexuronic Acids; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D065347:Hypromellose Derivatives; C006903:carbopol 940; D020723:Glucuronic Acid; D008747:Methylcellulose