Ketorolac tromethamine transdermal gel: development, in vitro and in vivo evaluation.
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 (AUC(0-t)) increased significantly with increasing dose, the effect on maximum serum concentration (C(max)) was insignificant. The formulation can be used for inflammatory pain management while avoiding gastric adverse events associated with oral ketorolac.
Dubey
Rajesh
R
Differentiated Products Division, Dr. Reddy's Laboratories Ltd., India. rajeshrrd@yahoo.com
Bommagani
Madhusudhan
M
Venkateswarlu
Vobalaboina
V
Mullangi
Ramesh
R
Karnati
Harinder R
HR
Thammera
Ranjith K
RK
Menon
Vinu C A
VC
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005782:Gels; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D020911:Ketorolac Tromethamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D023421:Models, Animal; D019301:Oleic Acid / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D005782:Gels; D012997:Solvents; D019301:Oleic Acid; D020911:Ketorolac Tromethamine; D004121:Dimethyl Sulfoxide