The Study Of Aceclofenac Ethosomal Gel

Aceclofena（cACF）is a new nonsteroidal antinflammatory drugs （NSAIDs） whichhas a significant effect on easing pain from osteoarthritis（OA） and rheumatoid（RA）．Asa moderately selective inhibitor of COX-2,ACF has less effect on on gastrointestinaltract than other NSAIDs.But due to its short half-life,the number of medication isincresaed and lead to strenouous fluctuation of plasma concenteation. It may bringadverse effects on gastrointestinal tract when orally administrated for a long time alsomake patients feel uncomfortable．The ethosomal system is a new transdermal drugdelivery carrier which attracted many attention and research in recent years．It iscomposed of phospholipid,high concent ethanol（20%-50%） and water，this systemwould be more effective for delivery of drugs into the various layers of the skin andeven into blood．Therefore，ethosomes and ethosomal gel were selected to carryaceclofenac for topical adminstration， it is not only reduce the side effects ongastrointestinal tract by oral drugs but also increase curative effect on local site．Pharmaceutical preformulation was taken to investigate some physico-chemicalcharacteristics of aceclofenac．The results shows that the solubility of aceclofenac inpH=7.4PBS was9817μg/mL and logP is0.72．With the increasing value of pH，thesolubility of aceclofenac increased，while the logP of aceclofenac is decreased．High-performance iquidhromatography（HPLC） method was developed for the invitro study of transdermal determination and the assay of aceclofenac ethosomes．Thedrug entrapment efficiency（EE） was determined by dialysis method．On the basis of the studies mentioned above，we choose the ethsnol infusion andhomogenization method to prepare aceclofenac ethosomes．According to the results ofsingle factor experiments，the amount of phospholipid and ethanol，drug dosage and thespeed of homogeneous were the main factors influence results．The optimal formulationselected by orthogonal design was evaluated by both EE and Cumulative percentage EEof the optimal formulation was48.0%． The physico-chemical characteristics and preliminary stability of aceclofenacethosomes was evaluated．The results of TEM showed that aceclofenac ethosomes wasa vesicle which has a thumbprint-like structure；The size of aceclofenac ethosomeswhich was determined by Zetasizer Nano ZS90was102nm；The average pH ofaceclofenac ethosomes was6.77．Results of the preliminary stability experimentsshowed that the aceclofenac ethosomes could be kept stable at4℃for3month withoutany signifiant changes．The transdermal delivery of aceclofenac ethosomes was studied and theSteady-state penetration rate was38.14μg cm^-2h^-1．While compared with aceclofenacethanol solution，the teansdermal flux of acelcofenac from ethosomes for24h was sixtimes higher than that form ethanol solution．On the basis of the studies mentioned above，carpobol980was used as gelbase．The concentration of base and the type and amount of penetration enhancers wasevaluated by Cumulative percentage in order to get the optimal formulation． Whilecompared with the ordinary aceclofenac gel made by myself，the Cumulative percentageof aceclofenac ethosomal gel was1.64times higher than that from the ordinaryaceclofenac gel．Results of the preliminary stability experiments showed that theaceclofenac ethosomal gel could be kept stable at4℃for3month without anysignifiant changes and the viscocity would change a lot while be kept at roomtemperature．Therefore，the optimal storage coditions of aceclofenac ethosomal was4℃．The irritancy of aceclofenac ethosomal gel on skin and the pharmacodynamicswere studied．The results proved that the aceclofenac ethosomal gel has no irritancy onskin，but excellent anti–inflammatory and analgesic effects．...