Preparation and pre-clinical characterization of sustainedrelease ketoprofen implants for the management of pain and inflammation in osteoarthritis

Purpose: To prepare and evaluate sustained-release ketoprofen implants for prolonged drug release and activity.Methods: Ketoprofen implants were prepared with poly (lactic-co-glycolic acid) (PLGA) and chitosan in the form of tablets. The implants were analyzed for drug loading, thickness, hardness, swelling, in vitro drug release, as well as in vivo analgesic and anti-inflammatory activities.Results: The implants were round, smooth in appearance, uniform in thickness and showed no cracks or physical defects on the surface. Their friability was < 1 % while drug content ranged from 89.98 ± 2.06 to 92.95 ± 1.65 %. In vitro drug release ranged from 70.23 to 92.04 % at the end of 5 days. Implants containing higher amounts of PLGA produced the highest swelling (40.24 ± 1.08 %). Implant IKT3 showed maximum analgesic activity (7.75 ± 1.00 s) and shortest time of maximum analgesia (2.5 h) in hot plate method. Inhibition of rat paw edema for IKT1, IKT2 and IKT3 was 79.95, 69.98 and 82.24 %, respectively, after 24 h.Conclusion: Ketoprofen-loaded implant IKT3 (4:4:2 ratio of PLGA, chitosan and ketoprofen) provides relatively quick onset and prolonged duration of analgesic effect. Thus, ketoprofen implants have a potential for development into therapeutic products for prolonged management of pain and inflammation in osteoarthritis.Keywords: Osteoarthritis, Ketoprofen implant, Prolonged analgesia, Poly(lactic-co-glycolic acid), Chitosa