The Application Of Hydroxyl Acrylic Pressure Sensitive Adhesive-Drug Interaction In Transdermal Drug Delivery System Design

Purposes:Pressure sensitive adhesives(PSAs)are the key excipient in the transdermal drug delivery system(TDDS).But the interaction between drug and PSAs are not clear,which leads the blindness of formulation design and hinder the development of TDDS.The present study was focus on the influence of interaction between drug and PSA and the relevant mechanism.The purposes of this study were to clarify the controlled release mechanism of hydroxyl group and the application scope;clarify the influence of drug physiochemical properties on drug solubility and release;clarify molecular mechanism of the mechanical property variation of drug-loaded PSA;provide the theoretical references for the design of TDDS and synthesis of hydroxyl PSA.Methods:Three monomers were used to synthesize the hydroxyl PSA and the difference with other PSAs was the focus of the study.Drug-PSAs miscibility,drug release behavior and skin permeation behavior were used as assessment criteria to clarify the application scope of hydroxyl PSA.Correlation analysis was built between drug release behavior and drug physicochemical parameters.In addition,rheometer and FT-IR was used to characterize the mechanical property variation mechanism of drug-loaded PSA.At last,single factor analysis was used to observe the influence of formulation factors of hydroxyl PSA.An optimized TDDS formulation was obtained through the optimization of PSA synthesis.Results:For the basic drugs,the control release ability of hydroxyl PSA was weaker than carboxyl PSA and similar with the non-functional PSA.The controlled release ability was reflected on the release dynamics.In the low drug loading,hydrogen bonding was the main controlling force and in the high drug loading,dipole-dipole interaction became the main factor.The interruption effect of drug on the hydrogen bonding and dipole-dipole interaction between PSA molecules was the reason that drug-loaded PSA lost its cohesion force.Increasing the hydroxyl group content was able to increase drug-PSA miscibility and thus increase the drug skin permeation amount.Conclusions:Hydroxyl PSA was sort of PSAs with excellent properties,which exhibited good drug miscibility and proper controlled release ability.Except hydrogen bonding,dipole-dipole interaction was another important factor that influenced the drug release behaviors.The interruption of both hydrogen bonding and dipole-dipole interaction was the main reason that drug loaded PSA losing its cohesion force.The adjustment of PSA synthesis was able to increase the drug miscibility and the skin permeation amount.It will provide theoretical reference for the development of TDDS and the synthesis of hydroxyl PSA.