Ketorolac Tromethamine Transdermal Gel: Development, In Vitro and In Vivo Evaluation

• Published in: Journal of pain & palliative care pharmacotherapy 2009, Vol.23 (1), p.26-34
• Main Authors: Dubey, Rajesh, Bommagani, Madhusudhan, Venkateswarlu, Vobalaboina, Mullangi, Ramesh, Karnati, Harinder R., Thammera, Ranjith K., Menon, Vinu C. A.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Chromatography, Liquid; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - blood; Cyclooxygenase Inhibitors - pharmacokinetics; Dimethyl Sulfoxide - pharmacology; dose ranging; Dose-Response Relationship, Drug; Drug Evaluation; Gels; Hydrogen-Ion Concentration; In Vitro Techniques; ketorolac tromethamine; Ketorolac Tromethamine - administration & dosage; Ketorolac Tromethamine - blood; Ketorolac Tromethamine - pharmacokinetics; Male; Models, Animal; nociceptive; Oleic Acid - pharmacology; Pain - drug therapy; Rats; Rats, Wistar; Skin Absorption - drug effects; skin penetrant; Solvents - pharmacology; transdermal gel
• ISSN: 1536-0288; 1536-0539
• DOI: 10.1080/15360280902728062

The authors developed and evaluated a transdermal gel formulation of ketorolac tromethamine (ketorolac) for the treatment of nociceptive somatic pain. The formulation was optimized for skin permeation enhancers, pH of the system, and dosage strength using in vitro and in vivo techniques. Of the various permeation enhancers evaluated, dimethyl sulfoxide (DMSO) and oleic acid were found to significantly increase skin permeation flux of ketorolac. The concentration of DMSO affected the rate as well as extent of transdermal absorption. Use of citric acid further improved the skin penetration of ketorolac. In vitro diffusion results indicated significant increase in drug permeation with increasing drug concentration. However, the same did not translate into higher skin permeation during in vivo study. Although the area under concentration time curve (AUC0-t) increased significantly with increasing dose, the effect on maximum serum concentration (Cmax) was insignificant. The formulation can be used for inflammatory pain management while avoiding gastric adverse events associated with oral ketorolac.