Study On Amphiphilic Hot-melt Pressure Sensitive Adhesives For Transdermal Drug Delivery Of Chinese Medicine

Styrene-isoprene-styrene block copolymer (SIS), C5 resin and other small molecular additives can be melt-blended to prepare hot-melt pressure sensitive adhesive (HMPSA) for transdermal drug delivery system. Because traditional SIS HMPSA is lipophilic, it can only improve the transdermal delivery of lipophilic drugs. In this study, to meet the requirement of Chinese medicines (including lipophilic and hydrophilic ingredients), amphiphilic HMPSA were fabricated by physical blending and chemical modified methods. The amphiphilic polymer skeleton provides release channels for lipophilic and hydrophilic drugs. The main work was carried out as follow:Firstly, SIS, poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride) (RLPO) and other small molecular additives were melt-blended to prepare SIS/RLPO HMPSA. On the basis of various experiment conditions, their optimization conditions were identified by studying the effect of small molecular additives on the microscopic structure and adhesive performance. The experimental results showed that when the molecular weight of polyethylene glycol (PEG) was 2000, the HMPSA had the appropriate adhesive performance and the lower fabricated tempersture, such as softening point 84.9℃, holding power>48h,180°peel strength 0.11KN/m. It was found that PEG-2000/RLPO=80/100(wt/wt), mineral oil/C5 resin/SIS=2/5/3(wt/wt/wt) and Dioctyl phthalate (DOP)/SIS=16/100(wt/wt), could be utilized to prepare HMPSA with good properties.Secondly, experiments were designed to study the effects of SIS/RLPO proportion on the microscopic structure, glass transition temperature (Tg), adhesion performance and transdermal drug delivery. The experimental results showed that:when the proportion of SIS/RLPO=1/2(wt/wt), the bi-continuous phase structure was formed. To some extent, the PS phase of SIS is partially compatible with RLPO phase, which might be demonstrated with thermal analysis. SIS/RLPO compounds had only one Tg peak in the high temperature region. With the increment of RLPO dosage, SIS/RLPO HMPSA adhesive performance was slightly reduced. The introduction of RLPO might be beneficial to the form of bi-continuous phase structure and provide the hydrophilic channels. With the increment of RLPO dosage, the cumulative release rate of lipophilic drug was reduced, but the cumulative release rate of amphiphilic drug and hydrophilic drugs were improved, gradually. Finally, the epoxidation of SIS with formic acid and hydrogen peroxide was studied. The microscopic structure of epoxidised SIS (ESIS) was characterized by Fourier Transform Infrared (FT-IR),1H nucleal magnetic resonance(1HNMR), Gel Permeation Chromatography (GPC), Different Scanning Calorimetry (DSC), Atomic Force Microscopy (AFM), and the adhesive performance and drug delivery behaviour of ESIS HMPSA were also discussed. The experimental results showed that:the epoxidation reaction mainly occurred in 1,4-isoprene units, and the molecular weight of ESIS and Tg of PI segment were increased gradually with the increase of the epoxy degree. The polarity of HMPSA increased due to epoxidation, which benefits to the improvement of HMPSA adhesive performance. Meanwhile, the cumulative release rate of the hydrophilic drug was up to 30% from 0%.