Department of Pharmaceutical Sciences, Università degli Studi di Milano, via G. Colombo 71, 20133 Milan, Italy.
Department of Chemistry, Università degli Studi di Milano, Via Golgi, 19-20133 Milan, Italy; CRC Materiali Polimerici (LaMPo), Department of Chemistry, Università degli Studi di Milano, Via Golgi, 19-20133 Milan, Italy.
Int J Pharm. 2020 Aug 30;586:119607. doi: 10.1016/j.ijpharm.2020.119607. Epub 2020 Jul 8.
This work aimed to design low-melting pressure sensitive adhesives and to demonstrate the feasibility of the preparation of (trans)dermal patches by hot-melt ram extrusion printing. This approach allows defining both the geometry of (trans)dermal patch and the drug strength easily according to patient needs. The preparation steps are the mixing of a poly-ammonium methacrylate polymer (i.e. Eudragit RL and RS) with a suitable amount of plasticizer (triacetin or tributyl citrate) and drug (ketoprofen or nicotine), the melting in the ram extruder, and the printing on the backing layer foil. The formulations were characterized in terms of rheological and adhesive properties, in vitro drug release and skin permeation profiles. The (trans)dermal patches made of Eudragit RL or Eudragit RS plasticized with the 40% triacetin could be printed at 90 °C giving formulations with suitable adhesive properties and without cold flow after 1 month of storage at 40 °C. Furthermore, the overall results showed that the performances of printed (trans)dermal patches overlapped those made by solvent casting, suggesting that the proposed solvent-free technology can be useful to treat cutaneous pathologies when the availability of (trans)dermal patches with size and shape that perfectly fit with the skin area affected by the disease improves the safety of the pharmacological treatment.
本工作旨在设计低熔融压力敏感型胶粘剂,并展示热熔挤模印刷法制备(透)皮贴片的可行性。该方法可根据患者需求轻松定义(透)皮贴片的几何形状和药物强度。制备步骤包括将聚甲基丙烯酰胺聚合物(即 Eudragit RL 和 RS)与适量的增塑剂(三醋酸甘油酯或柠檬酸三丁酯)和药物(酮洛芬或尼古丁)混合、在挤模机中熔融、以及在背衬箔上打印。对制剂进行了流变学和粘附性能、体外药物释放和皮肤渗透特性的表征。用 40%三醋酸甘油酯增塑的 Eudragit RL 或 Eudragit RS 制成的(透)皮贴片可在 90°C 下打印,得到的制剂具有合适的粘附性能,在 40°C 下储存 1 个月后无冷流。此外,整体结果表明,打印(透)皮贴片的性能与溶剂浇铸法相当,这表明,当可获得与受疾病影响的皮肤区域完全匹配的尺寸和形状的(透)皮贴片时,这种无溶剂技术可有助于治疗皮肤疾病,从而提高药物治疗的安全性。