Dubey Rajesh, Bommagani Madhusudhan, Venkateswarlu Vobalaboina, Mullangi Ramesh, Karnati Harinder R, Thammera Ranjith K, Menon Vinu C A
Differentiated Products Division, Dr. Reddy's Laboratories Ltd., India.
J Pain Palliat Care Pharmacother. 2009;23(1):26-34. 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 (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.
作者研发并评估了用于治疗伤害性躯体疼痛的酮咯酸氨丁三醇（酮咯酸）透皮凝胶制剂。使用体外和体内技术，针对皮肤渗透促进剂、体系pH值和剂量强度对该制剂进行了优化。在评估的各种渗透促进剂中，发现二甲基亚砜（DMSO）和油酸可显著增加酮咯酸的皮肤渗透通量。DMSO的浓度影响透皮吸收的速率和程度。柠檬酸的使用进一步改善了酮咯酸的皮肤渗透。体外扩散结果表明，随着药物浓度增加，药物渗透显著增加。然而，在体内研究中，同样的情况并未转化为更高的皮肤渗透。尽管浓度-时间曲线下面积（AUC(0-t)）随剂量增加而显著增加，但对最大血清浓度（C(max)）的影响不显著。该制剂可用于炎性疼痛管理，同时避免与口服酮咯酸相关的胃部不良事件。
