The Effect Of Hot Melt Pressure Sensitive Adhesive Formulation On The Percutaneous Penetration Of Drugs In Vitro

Hot-melt pressure-sensitive adhesive is a solvent-free solid adhesive,which is considered to be one of the new dosage forms of transdermal drug delivery systems.Its properties of heating and melting and curing at room temperature make it have strong adhesion to the skin and can be easily peeled from the skin surface without damaging the skin structure,which improves the patient’s compliance.In recent years,there have been many studies on the adhesive performance of different formulations on patches,but there are few reports on the release of drugs in pressure-sensitive adhesives with different formulations.In this regard,this study chose diacerein,diacerein-N₁₂ion pair,strychnine and strychnine-C₁₀ion pair as model drugs,and explored the different types of hot melt pressure sensitive adhesive formulations through in vitro transdermal The effects of thermoplastic elastomers,plasticizers and viscosity-enhancing agents on the percutaneous penetration of drugs in vitro,and molecular simulations were used to explore their mechanisms at the molecular level.First,the model drug is added to the hot melt pressure sensitive adhesive prepared by naphthenic oil,hydrogenated C₅and different types of thermoplastic elastomers to prepare the tested patch.The results of in vitro transdermal penetration experiments show that when the thermoplastic elastomer is 3421,the 14-hour cumulative penetration of diacerein,diacerein-N₁₂ion pair,strychnine and strychnine-C₁₀ion pair are all The maximum values are 0.111±0.020μg/cm²,0.211±0.102μg/cm²,7.906±0.903μg/cm²and 8.789±1.178μg/cm².Then use 3421hydrogenated C₅and add different plasticizers to prepare hot melt pressure-sensitive adhesives,and add model drugs to prepare patches.The in vitro transdermal penetration test results show that when liquid paraffin is used as plasticizer,diacerein and diacetin The 14-hour cumulative transdermal volume of Rein-N₁₂ion pair reached the maximum value of 0.469±0.048μg/cm²and 1.014±0.011μg/cm²;When polyisobutylene is used as a plasticizer,the 14-hour cumulative transdermal penetration of strychnine and strychnine-C10 ion pairs reaches the maximum value of28.500±3.272μg/cm²and 28.500±3.272μg/cm².Secondly,the tackifier was discussed,and 3421 was selected as the thermoplastic elastomer.When the model drug is diacerein and diacerein-N₁₂ion pair,liquid paraffin was selected as the plasticizer to explore hydrogenated C₅,The effect of terpene resin T100 and tackifying resin 138 on its in vitro percutaneous penetration.The experimental results show that when the tackifying resin 138 is used as a tackifier,its 14-hour cumulative skin penetration rate can reach 2.104±0.398μg/cm²and 9.677±1.039μg/cm².When the model drug is strychnine and strychnine-C₁₀ion pair,polyisobutylene is selected as the plasticizer.The experimental results show that when hydrogenated C₅is used as a thickener,its14-hour cumulative transdermal penetration is the highest,reaching 28.500±3.272μg/cm²and 31.528±5.266μg/cm².In summary,when diacerein and diacerein-N₁₂ion pairs are used as model drugs,the optimal hot-melt pressure-sensitive adhesive formula is:3421 as a thermoplastic elastomer,liquid paraffin as a plasticizer,and tackifier Resin 138 is used as a tackifier;When strychnine and strychnine-C₁₀ion pairs are used as model drugs,the optimal hot-melt pressure-sensitive adhesive formulation is:3421 as a thermoplastic elastomer,polyisobutylene as a plasticizer,and hydrogenated C₅as a tackifier.Finally,this article uses molecular simulations to explore the mechanism of hot-melt pressure-sensitive adhesive formulations on the percutaneous penetration of drugs in vitro at the molecular level.First,the Blends module was used to mix the drugs and the hot melt pressure sensitive adhesives containing different thermoplastic elastomers.From the mixing energy diagram,it was found that the mixing energy of the drugs and the hot melt pressure sensitive adhesive with the thermoplastic elastomer 3421 was the largest.Then mix the medicine with hot melt pressure-sensitive adhesives containing different plasticizers.Diacerein and Diacerein-N₁₂have the largest mixing energy with the hot melt pressure-sensitive adhesives whose plasticizer is liquid paraffin;The mixing energy of strychnine and strychnine-C₁₀and the hot-melt pressure-sensitive adhesive whose plasticizer is polyisobutylene is the largest.Finally,the drug is mixed with hot melt pressure-sensitive adhesives containing different tackifiers.Diacerein and diacerein-N₁₂have the largest mixing energy with hot melt pressure-sensitive adhesives with tackifying resin 138 as the tackifier;The mixing energy of C₁₀and Strychnine-C₁₀and the hot-melt pressure-sensitive adhesive with hydrogenated C₅as tackifier is the largest.Therefore,the mixing energy affects the release of the drug.The greater the mixing energy of the system,the more unstable the system,and the easier it is for the drug to be released from the entire system.