Studies On Diclofenac Diethylamine Hydrogel Patch

Diclofenac diethylamine (DDEA) is one of powerful non-steroidal anti-inflammatory drugs (NSAIDs), which has been most commonly used to reduce inflammation and pain with many advantage such as less adverse reaction, small dose and little individual difference and so on. But the side effect of gastrointestinal tract and hepatic first pass effect, which result in that the bioavailability is only 50%, appears following chronic oral administration. In this paper, a new kind of patch named hydrophile hydrogel transdermal patch was prepared. The effect of penetration enhancers on percutaneous absorption of DDEA by experiment of in vitro transdermal permeation has been studied and the best transdermal enhancer was selected. The quality and in vitro drug release profile of DDEA hydrogel patch has been studied. The main results are as follows:1. DDEA hydrogel patches have been selected by L9(34)orthogonal and formulation optimization experiment. The prepared hydrogel patch has advantages of good moisture permeability and skin compatibility.2. The method for measuring its in vitro percutaneous permeability of DDEA has been established. The result of transdermal permeation experiment with isolated rat abdominal skin taken as a model by using modified Franz diffusion showed menthol used alone had the most obvious permeation-enhancing effect. There was a positively related dose-effect relationship of menthol from 1% to 5% on increasing the penetration of DDEA. The amount iontophoretic flux (Q) of the 3% , 5% menthol group both reached the Votalin Emulgel group after 24 hours. Comprehensively considered efficacy and cost, the 3% menthol could be choosed as the transdermal enhancer for DDEA hydrogel patch.3. HPLC method was selected by determination of content determination. Excipients avoid interference. DDEA had a good linear relationship in the scope of 10.04 50.20μg·mL^-1. It has high stability and good accuracy. The prepared hydrogel patch content uniformity.4. HPLC method was selected by determination of related substances. It showed that little related substances were produced after 2 hours in the condition of high temperature, 0.3%H2O2, strong acid, alkali and light. The conditions of the chromatographic separation of impurities were appropriate and the peak was good. The related substances in three batches of samples fulfilled the requirements. The prepared hydrogel patch had perfect plastic property and its mean content of ointment was 125.25 mg.5. The in vitro drug release profile of the prepared DDEA hydrogel patch was in accord with Higuchi equation. Its release degree could reach more than 80% after 10 hours and 98% within 24 hours, up to the requirement.