Design,Synthesis And In Vitro Drug Release Of Amphiphilic SIS-g-PEG Thermoplastic Elastomer

Hot-melt pressure-sensitive adhesive is the most widely used type of pressure-sensitive adhesive.It is solid at room temperature and has melt fluidity when the temperature rises.It is chemically stable,has the functions of storing drugs,controlling the release of drugs,and tightly adhering to the skin.It is an important part of the transdermal drug delivery system.The skeleton material of hot-melt pressure-sensitive adhesive is thermoplastic elastomer.The most common thermoplastic elastomer is styrene block copolymer,including polystyrene-isoprene-styrene(SIS)triblock copolymer,polystyrene-butadiene-styrene(SBS)triblock copolymers,etc.,SIS-type hot-melt pressure-sensitive adhesive prepared with SIS-type thermoplastic elastomer as the matrix has the characteristics of strong cohesion,high drug loading and good adhesion,but has the disadvantages of poor moisture absorption and permeability,low release rate of hydrophilic or low lipophilic drugs in vitro,and is easy to cause redness and other allergic reactions,which limits its large-scale promotion.Therefore,in this study,chemical graft modification of SIS thermoplastic elastomer was used to build more release channels for hydrophilic drugs,improve the hydrophilicity of the pressure-sensitive adhesive system,and select representative model drugs of hydrophilicity and lipophilicity to investigate in vitro drug release properties of thermoplastic elastomer films before and after modification.Firstly,epoxidized SIS was prepared by formic acid-hydrogen peroxide in-situ epoxidation using SIS-type thermoplastic elastomer,and then hydrophilic polyethylene glycol was introduced into the epoxy group of the epoxidized SIS by ring-opening grafting method to prepare the grafted SIS.Hydrogen nuclear magnetic resonance spectroscopy,fourier transform infrared spectroscopy and differential scanning calorimetry analysis methods were used to test and characterize their epoxidation degree,phase structure and compatibility,respectively.The epoxidation rate,grafting rate,functional group structure and characteristic peak assignment were determined through the spectrum,the compatibility between the phases in the thermoplastic elastomer is determined by the melting point change,and the thermoplastic elastomer matrix that meets the experimental conditions is prepared.Secondly,HPLC analysis methods which were suitable for the model drugs of paeoniflorin and oleanolic acid were established.The experimental results showed that the specificity and system applicability of the two analysis methods are good,with a good linear relationship and a good precision in a certain concentration range.The n-octanol-water partition coefficients of the two drugs were determined,the experimental results showed that paeoniflorin is more hydrophilic and oleanolic acid is more lipophilic.By examining the changes in the drug concentration of the two drugs in the rat skin homogenate over time,it is proved that the stabilities of the two drugs in human skin are better.Finally,select the representative hydrophilic drug paeoniflorin(glycoside compounds)and lipophilic drug oleanolic acid(triterpenoid compounds),study in vitro drug release properties of thermoplastic elastomers prepared from three different copolymers of SIS,epoxidized SIS as the matrix.The experimental results showed that,in the thermoplastic elastomer with epoxy groups and hydrophilic polyoxyethylene ether segments,the cumulative release rate of paeoniflorin at 24 h was increased from 0.13% to 7.45% and 4.21%,respectively,the cumulative release rate of oleanolic acid at 24 h was increased from 41.83% to 57.25% and 61.33%,respectively,demonstrating that both epoxidation treatment and grafting treatment can increase the polarity of the SIS copolymer,thereby enhancing the in vitro drug release performance of hydrophilic drugs and lipophilic drugs.