| Diacerein is a synthetic anthraquinone compound,which is clinically used to treat osteoarthritis and can effectively repair articular tissue.It is one of the drug that can effectively defer the progression of inflammation in the market currently.However,due to its poor water solubility,the oral bioavailability is only 3 5~56%with obvious gastrointestinal side effects ahead,limit its clinical application.Diacerein can directly tansport through the skin from the application site into the deep articular cavity by a transdermal delivery system,the oral side effects can be effectively avoided synchronously.However,diacerein is a lipophilic drug that doesn't easily penetrate through aqueous epidermis and needs to improve its skin permeability.The transdermal permeability of drugs can be significantly enhanced by ion-pair formation and chemical enhancers.In this study,Diacerein was developed into a patch use ion-pair and chemical enhancers as a dual strategy.First of all,the diacerein ion-pair complexes were prepared.It's found that with acetone as solvent,the molar ratio of diacerein to organic amines set as 1:3,stable products can be formed at room temperature.The water solubility of all prepared products is greatly improved and the Log P value was greatly reduced.The 1H-NMR tests showed that the chemical shift of proton e at the 2th position in all products showed upfield shifts compared with that in diacerein.FT-IR measurements showed that the absorption peak around 1693.44 cm-1 of products caused by C=O stretching vibrational in carboxyl group was red-shifted.The DSC test results showed that the melting point of products was significantly reduced compared to diacerein.All of above proved that the diacerein ion-pair complexes was prepared successfully.Secondly,In vitro transdermal experiment was used to investigate the percutaneous permeability of diacerein and its ion-pair complexes in solution system,and the formulation of diacerein ion-pair patch was optimized.The results showed that the formation of ion-pair between diacerein and organic amines can effectively promote the percutaneous penetration of diacerein,in which the ER of ion-pair formed by diacerein and triethanolamine(DCN-TETA)was the highest,reaching 4.30 folds.The optimal prescription of diacerein ion-pair patch is:SJ hot melt pressure sensitive adhesive as matrix,with 3%lauric acid and 5%DCN-TETA(w/w)drug loading.Finally,the quality of diacerein ion-pair patch was investigated.The results showed that the paste contained of the patch were 73.50±0.9%;The RSD of patch sample's weight was 2.00%;The moisture permeability of the patch reached 10.65±0.53g/cm2/d;The initial adhesion test results showed that the maximum number of steel ball adhered to the patch was No.15;The holding power test results showed that the patch peeled off from the test board was taken more than 48 hours;The drug content of the patch is 52.90±1.31?g/cm2;The drug release rates of 5%drug-loading 87-4098 PSA patch and 5%drug-loading SJ hot-melt PSA patch were as follows:11.45±0.32%and 18.20±0.26%,respectively.Both were consistent with the Higuich drug release model,with the linear equations were Q%=2.7453t1/2-2.6592,R2=0.9742 and Q%=4.4987t1/2-4.9410,R2=0.9801,respectively.The above results indicate that the quality of the diacerein ion-pair patch is controllable. |
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