Topical dosage form of valdecoxib: preparation and pharmacological evaluation.
Valdecoxib, a selective COX-2 inhibitor, produces serious side effects when given orally. This has led to its withdrawal. Topical application of valdecoxib was formulated and evaluated for its efficacy and safety. Standard procedures were followed and male Wistar albino rats were used to test the anti-inflammatory effect and effect in hyperalgesic conditions. Ointments, creams, and gels containing valdecoxib 1% (m/m) were prepared. These were tested for physical appearance, pH, spreadability, drug content uniformity, in vitro diffusion. Gel prepared using Carbopol 940 (F-X) was selected after the analysis of the results. Formulation F-X was evaluated for acute skin irritancy, anti-inflammatory effect, optimum effective concentration of valdecoxib, effect on hyperalgesia, inhibition of the granulation tissue formation and anti-arthritic effect. Determination of valdecoxib in test animals plasma and determining the blood clotting time and bleeding time were conducted to study the safety of topical valdecoxib. Valdecoxib gel containing 1% (m/m) of the drug was significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to placebo gel, but exhibited significantly (p < 0.05) lower suppression of inflammation than commercial rofecoxib gel. Concentration of valdecoxib used in the preparation minimizes the risk of systemic effects, as shown by the analysis of rat plasma for the presence of valdecoxib; hence, this may be the alternative to oral preparations. The bleeding and clotting time showed no significant difference before and after application of F-X.
Kesavanarayanan
K S
KS
C.L. Baid Metha College of Pharmacy, Thoraipakkam, Chennai-600096, India.
Nappinnai
Mohanavelu
M
Ilavarasan
Raju
R
D000180:Acrylic Resins / Q000737:chemistry; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D002351:Carrageenan / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005782:Gels; D006614:Hindlimb; D006863:Hydrogen-Ion Concentration; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009824:Ointments; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D023422:Skin Irritancy Tests / Q000379:methods; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties; D013997:Time Factors; D016896:Treatment Outcome; D000096926:Benzenesulfonamides
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D005782:Gels; D007555:Isoxazoles; D009824:Ointments; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C006903:carbopol 940