Topical dosage form of valdecoxib: Preparation and pharmacological evaluation

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. Topical dosage form of valdecoxib: Preparation and pharmacological evaluation Valdekoksib, selektivni COX-2 inhibitor, primijenjen peroralno urokuje ozbiljne nuspojave, zbog čega je povučen iz uporabe. U ovom radu izraďen je i evaluiran pripravak valdekoksiba za topičku primjenu. Uporabljeni su standardni postupci za procjenjivanje protuupalnog i analgetskog djelovanja na muškim Wistar albino štakorima. Prireďene su masti, kreme i gelovi s udjelom valdekoksiba od 1% (m/m) kojima je procijenjen fizički izgled, pH, mazivost, ujednačenost sadržaja ljekovite tvari, in vitro difuzija. Nakon analize rezultata, za farmakološka ispitivanja je izabran gel s Carbopol 940 (F-X). Procijenjena je akutna iritacija kože tog pripravka, njegov protuupalni učinak, optimalna koncentracija valdekoksiba, učinak na stanje hiperalgezije, inhibicija stvaranja granulocita i antiartritični učinak. Za procjenu sigurnosti topičke primjene valdekoksiba, odreďena je njegova koncentracija u krvnoj plazmi, te vrijeme zgrušavanja krvi. Gel s udjelom valdekoksiba 1% (m/m) imao je značajno veći učinak u inhibiciji hiperalgezije povezane s upalom (p < 0,05) nego placebo pripravak, ali je imao značajno manji učinak (p < 0,05) od gela s rofekoksibom. Analiza plazme na prisutnost valdekoksiba ukazuje na niski rizik sistemskog učinka. Vrijeme krvarenja i zgrušavanja nije se bitno promijenilo prije i poslije uporabe F-X. Zbog toga bi ovaj pripravak mogao biti alternativa peroralnim pripravcima.