Chronobiological and chronopharmacological studies of ketoprofen and its solid dispersion form using adjuvant arthritis model in rats.

Chronobiology of rheumatoid arthritis (RA) was studied using a standard adjuvant arthritis animal model. Chronopharmacology of ketoprofen, and its solid dispersion forms was also studied. Temporal variations in the degree of articular inflammation (paw volume) and progression of articular destruction were studied by injecting Freund's Complete Adjuvant (FCA) at 0800 and 2000 hrs. Temporal variations in anti-inflammatory effects and ulcerogenic effect were also studied by administration of plain ketoprofen (20 mg/kg) and its solid dispersion with hydroxypropyl beta-cyclodextrin (equivalent to 20 mg/kg of ketoprofen) at the same time points (0800 and 2000 hrs) twice weekly for 22 days. Solid dispersion of ketoprofen was found to be more effective in inhibiting progression of RA. The incidence and severity of ulcers was found to be less with the solid dispersion. The protective effect of ketoprofen and its solid dispersion was significantly higher when these were administered at 0800 hrs. The incidence of ulceration was more in 2000 hrs group. Thus, it was observed that in the adjuvant induced arthritis model, inflammation and articular damage was significantly greater in the rest period of diurnally active rats than in the activity phase. KPF and its solid dispersion showed better protection from inflammation in the morning than in the evening.