The Study On Supersaturation Of Donepezil Transdermal Patch

Since Donepezil also causes gastrointestinal adverse effects,a transdermal delivery system might be a suitable method to overcome the problems of conventional oral administration of Donepezil.The donepezil transdermal patch was prepared with the polyacrylate pressure sensitive adhesive,and the supersaturation state in the preparation,release and permeation of transdermal patch was studied.The permeability of donepezil and donepezil HCl across isolated rat abdomen skin was examined.The steady-state permeation rates of donepezil hydrochloride and donepezil were 1.4 ?g/cm~2/h,5.1 ?g/cm~2/h,respectively.As expected the permeation amount of donepezil base was significantly higher than that of donepezil HCl.Accordingly,further studies were conducted using donepezil.Secondly,transdermal patch process factors(thickness,curing time and curing temperature)and formulation factors(loading,pressure sensitive adhesive)were investigated using coating performance and stability as the main index.The results showed that the solid content of 25%-35%,three kinds of PASs can be successfully coated,and the dry film thickness and solid content had no obvious relationship,which is mainly decided by the coating thickness of wet film,therefore solid content of 30% was determined for coating.Saturated loading of donepezil in Duro-Tak 87-4098 in,Duro-Tak 87-2287 and Duro-Tak 87-2852 were 25%,50%,20%(w/w),respectively.However,the saturated loading would decrease because preparation process will cause DNPZ recrystallization,thus,for patch stability,drug loading is only reached 20%,30%,15%(w/w),respectively.Finally,Duro-Tak 87-2852(carboxyl functional group),which is highly tolerance to enhancers,was used as carrier to prepare transdermal patch.5% crystallization inhibitor Soluplus,HMPCAS-MF and accelerant oleic acid,polyethyleneimine,stearyl alcohol,LABRASOL,LABRAFIL M 1944 CS were added separately.In-vitro release and permeation test were performed to study the drug release and permeation mechanism of transdermal patch.The results showed that the addition of stearyl alcohol significantly promoted the release of drug from the transdermal patch,the cumulative release rate increased 88.9%,but the cumulative permeation percent increased only 73.5%,LABRASOL decreased the cumulative release by 19.6% while increased the cumulative permeation percent 94.1%;HPMCAS-MF was able to keep the steady rate of donepezil release from the patch.which the cumulative transmittance decreased by 15.3%,the cumulative transmittance was 52.9%,conversely.In summary,crystallization inhibitors avoid drug released from the patch recrystallized in the diffusion layer;releasing enhancers improve the amount of drug release from the patch to stay high concentration gradient to the skin.The permeation enhancers such as oleic acids can enhance the drug release from the transdermal patch,but also improve the skin permeation,kept the steady state both in Transdermal patch-Diffusion layer and Diffusion layer-Skin avoiding drug recrystallized in the diffusion layer.