Application Of Novel Controlled Release Membranes In ISDN Transdermal System

As one of the novel approaches of drug delivery, transdermal drug delivery system offers more advantages than conventional administrations, including avoiding the first-pass metabolism, longer duration of therapeutic action, reduction side effects, improving patient compliance, and so on. Therefore transdermal drug delivery system has been one of the prospective fields. In the previous study, UV photosynthesis was utilized in preparing the new types of controlled release membranes successfully. In this study, the application of novel controlled release membrane in isosorbide dinitrate (ISDN) transdermal administration was researched.Firstly, in order to find the optimized controlled release membrane, nine different copolymer membranes were used as alternatives, which were used in transdermal experiment to investigate their permeability for ISDN in different concentrations. The result showed that all of the nine copolymer membranes could control drug permeation in zero order. Moreover, the permeation rate J linearly increased with the increase of drug concentration. For ABC7 membrane had the best permeation property for ISDN, it was regarded as the optimized controlled release membrane.In order to screen out appropriate drug reservoir matrix, ethyl cellulose (EC) and polyvinyl alcohol (PVA), which had different properties, were selected as options. The drug reservoirs, which contained ISDN in 9.5%, were made by EC and PVA respectively. The films of drug reservoirs were covered on ABC7 membranes tightly to study the permeation property. The result showed that ABC7 membrane could control drug release in zero order, there were no burst release, and the permeation rate was better when PVA was used as matrix. Thus, PVA was considered as the appropriate matrix for drug reservoir.In order to screen out appropriate penetration enhancer, oleic acid, urea and propylene glycol were selected as options. The films of ISDN reservoirs, which contained penetration enhancers, PVA and ISDN in certain ratios, were prepared. In order to study the influence of penetration enhancers on ABC7 membrane and the excised rat skin, the films were covered on ABC7 membrane and the excised rat skin tightly to be used in the in vitro transdermal experiment, and the films without penetration enhancer was used as a control. The result showed that penetration enhancers had no significant influence on ABC7 membrane's permeability, but they influenced the excised rat skin's permeability observably. And when urea was used as penetration enhancer, the excised rat skin had the best permeation property, so urea was considered as the optimized penetration enhancer. Then ABC7 membrane was clamped between the film of drug reservoir (containing urea) and the excised rat skin to be used in transdermal experiment. The result showed that ABC7 membrane could control drug release in zero order, and there was no burst release, the cumulative drug permeation was linearly dependent on time.A kind of hydrophilic pressure sensitive adhesives (PSAs), which was made of polyvinyl pyrrolidone (PVP), gelatin and polyethylene glycol 400 (PEG400), was utilized in this study. ABC7 membrane was sandwiched between drug reservoir films and PSAs to form a primary ISDN-tape. The permeation property of this primary ISDN-tape, which was covered on the excised rat skin tightly, was studied. The result showed that ABC7 membrane could control drug release in zero order, and there were no burst release, the cumulative drug permeation was linearly dependent on time. But the permeation rate decreased, because PSAs could control drug release. In order to resolve this problem, a few of ISDN was dispersed into PSAs. A new ISDN-tape which was consisted of PSAs containing ISDN,ABC7 membrane and drug reservoir containing urea was prepared. The permeation property of this new ISDN-tape, which was covered on the excised rat skin tightly, was studied. The result showed that ABC7 membrane could control drug release in zero order, and there was no burst release, the cumulative drug permeation was linearly dependent on time. Moreover, the value of permeation rate was higher than that of primary ISDN-tape.The permeation rates of Frandol? tape and above-mentioned ISDN-tape were compared with each other. The result showed that both patches could control the drug release in zero order, and there was no burst release, the cumulative drug permeation was linearly dependent on time. Moreover, both of their values of permeation rates and 48hrs cumulative drug permeation were close.In conclusion, a new ISDN-tape, which was consisted of PVA drug reservoir (containing urea as penetration enhancer),ABC7 membrane and PSAs (containing ISDN), was prepared successfully. This new ISDN-tape has similar results of in vitro transdermal experiment with Frandol? tape. So it's feasible to introduce this novel controlled release membrane to ISDN TDDS.