Date of Award
Master of Science (MS)
Ketorolac tromethamine is a non-steroidal drug that has potent analgesic and moderate anti-inflammatory activity. A single dose of ketorolac tromethamine is clinically more effective than that of many drugs in the management of moderate to severe postoperative pain. Transdermal delivery of ketorolac tromethamine seems as a potential method of administration that would be non-invasive and eliminate repeated dosing regimens. Although a transdermal dosage form of ketorolac has not arrived in the market, permeation enhancement of ketorolac tromethamine transdermally and topically has been the subject of several pharmaceutical research studies.
The objective of this study was to evaluate the possible release enhancement effects of several commonly used skin emollient substances on the in vitro release of ketorolac tromethamine from topical emulsion formulations. The O/W emulsions containing 1.65% ketorolac tromethamine were prepared as topical formulations. Six different emulsions with three different emollients; sucrose polysoyate, di-ppg-2-myreth- 10 adipate, and ppg-3-benzyl myristate at 1 and 5% levels were prepared. The release of ketorolac tromethamine from each emulsion was studied in vitro using static Franz diffusion cells. The diffusion studies were conducted across cellulose ester and silicone membranes. A validated HPLC assay method was used to analyze the drug concentration. A linear mixed-effect model was used to test the statistical significance of all the release rates from the six emulsions compared to the control at a significance level of p
The release experiment results show that sucrose polysoyate significantly increased the release rate of ketorolac tromethamine both at 1 and 5% levels across the silicone membrane, although it increased the release rate of the drug only at 5% ratio across the cellulose ester membrane. According to the rheological analysis results, addition of sucrose polysoyate at 5% level increased the complex viscosity and the thixotropy values. Di-ppg-2-myreth-10 adipate also increased the release rate of the drug both at 1 and 5% levels across the silicone membrane, however it had no effect on the release rate of the drug at 1 % and significantly decreased the release rate of the drug at the 5% concentration across the cellulose ester membrane. The addition of di-ppg-2- myreth-l 0 adipate both at 1 and 5% concentrations showed a decrease in the complex viscosity and the thixotropy values. PPG-3- benzyl myristate increased the release rate of ketorolac tromethamine both at I and 5% concentrations across the cellulose ester and the silicone membrane. PPG-3-benzyl myristate, at 1 % level increased the complex viscosity and the thixotropy value however it had no effect on the viscosity, and lowered the thixotropy at 5% level.
Our in vitro test results helped us understand how the skin emollients may affect the diffusion rate of ketorolac tromethamine out of topical formulations and as O/W emulsions across two different membranes. It also gave us an idea whether these emollient substances could be studied and evaluated further as potential permeation enhancers for in vivo studies. Further, this research identified the inadvertent effect that emollient excipients may have on the permeation of other components when used for their emollient effect in various skin preparations.
Alioglu, Burcak, "In Vitro Effects of Emollient Substances on Release of Ketorolac Tromethamine" (2008). Open Access Master's Theses. Paper 1028.