Synthesis Of Naproxen Derivatives And Investigation Of It Transdermal Delivery Systerm

Naproxen is a propionic acid derivative with analgesic and anti-inflammatoryactivity which has been widely used in the treatment of rheumatoid arthritis. Whilethe huge irritant to gastrointestinal tract and potential cardiovascular risks limitthe clinical application, its poor solubility in water, low oral bioavailability alsokeep it from being widely used. Rheumatoid arthritis is an autoimmune diseaserequiring long-term drug delivery, in order to improve the bioavailability ofnaproxen in clinical application, avoid gastrointestinal irritation and toxic actionin cardiovascular reduced by conventional administration, provide a long-lastingdrug with well security、High bioavailability for rheumatoid arthritis? we intendsto reform the structure of naproxen, and select a suitable transdermal drug deliverysystem to avoidoral dosing of side effects in gastrointestinal and cardiovascular,reduce side effects and increase effectiveness.The main contents were sunmmarized as following:1.Synthesized a series naproxen ester derivatives and characterized theirstructures by1H NMR, UV, MS and Elemental analysis.2.Four kinds of different substrates of transdernal drug delivery system withnaproxen and its esters derivatives was prepared, and the stability of thepreparation was investigated. The results show the four kinds of transdernal drugdelivery system have good stability.3.We used Franz-type diffusion cells to carried out a preliminary study on therelease ability of four kinds of transdernal drug delivery system with naproxen andits four ester derivatives In vitro，And the release data was fitted into threedifferent model. The result shows that the effect of compounds’ structure to drugrelease was not obvious, while matrix has a relatively large impact on the releaseof the drug (CMC-Na> sodium alginate> Carbomer> ointment). At the same time,the statistical analysis shows each transdernal drug delivery system with naproxenand its four ester derivatives have the same release pattern. And the drug release inthe time level and the matrix level have significant difference，and repeatedmeasures analysis results also show that the matrix and time has a significantinteraction effect.4.Select the abdominal skin of mice as a permeable membrane, naproxen ester derivatives were investigated by transdermal release homemade skin preparation.The results show that the compound structure has little impact on the transdermalabsorption of drugs, while the matrix shows a relatively affect with the transdermalabsorption of the drug (CMC-Na> sodium alginate> carbomer> ointment), thestatistical analysis shows that each transdernal drug delivery system with naproxenand its four ester derivatives have the same transdermally absorbable, in the levelof preparation and time, Transdermal absorption of drugs have significantdifference，and repeated measures analysis results also show that the matrix andtime has a significant interaction effect.The local release of drug in the tissues of the body was further evaluated.Explore the different chemical structures and pharmaceutical preparations on theability of penetrate to the skin provide a research foundation for Naproxen and itsderivatives developed into a topical long-lasting administration preparation withhigh curative effect, less side effects.