Penetration Enhancement Effect of Turpentine Oil on Transdermal Film of Ketorolac

Purpose: To prepare transdermal films of ketorolac tromethamine (KT) and study the effect of turpentine oil as a penetration enhancer for the drug.
Methods: Transdermal films of KT were prepared with Carbopol-934 and ethyl cellulose, with turpentine oil as the penetration enhancer, using solvent evaporation method. The films were characterized for physicochemical properties, ex vivo permeation, as well as in vivo anti-inflammatory and analgesic activities in Wistar rats.
Results: The transdermal films were uniform in weight and thickness, flat, with high drug content (93.9 to 98.5 %) and of high folding endurance (134.0 to 180.0). Drug permeation through excised rat abdominal skin was prolonged, with the total drug release ranging from 58.88 to 88.98 % in 24 h. The films containing penetration enhancer showed higher drug permeation than the one without the enhancer; furthermore, drug permeation increased with increase in the concentration of the enhancer. The films were non-irritant to the skin. The transdermal films prepared with permeation enhancers showed greater anti-inflammatory activity (87.55 ± 2.50 and 83.24 ± 2.29 % inhibition of rat paw edema at the end of 12 h for formulations F2 and F3, respectively, compared to that of the formulation without enhancer with 69.99 %) as well as greater analgesic activity (quicker onset of analgesia in 1.5 h with longer duration of 10 to 12 h).
Conclusion: Transdermal films of ketorolac have a potential for use in the treatment of pain and inflammation. Incorporation of turpentine oil in the films enhances not only drug flux but also analgesic and anti-inflammatory activities in rats.

Keywords
Transdermal patch; Spinal cord injury; Ketorolac; Analgesic; Anti-inflammatory; Penetration enhancer; Turpentine oil