Acta Pharm. 57
(2007) 199-209
Original research paper
Topical dosage form of valdecoxib: Preparation and pharmacological evaluation
K. S.
KESAVANARAYANAN, MOHANAVELU NAPPINNAI AND RAJU ILAVARASAN*
arilavarasan@yahoo.co.in
Department
of Pharmacology, C. L. Baid Metha
College of Pharmacy, Thoraipakkam, Chennai-600096. India
Accepted February 16, 2007
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 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.
Keywords: valdecoxib, topical gel, in vitro, in vivo evaluation