Pharmaceutical Innovation and Development Group (PIDG), Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Central Adelaide Local Health Network, The Queen Elizabeth Hospital, Woodville, SA 5011, Australia.
Int J Pharm. 2022 Jan 5;611:121316. doi: 10.1016/j.ijpharm.2021.121316. Epub 2021 Nov 25.
Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC.
含 5-氟尿嘧啶 (5-FU) 的贴剂是克服商业乳膏在治疗非黑素瘤皮肤癌 (NMSC) 方面不足的一种可行选择。增塑剂是药物粘附 (DIA) 贴剂的关键组成部分，因为它们可以显著影响贴剂的机械性能、粘性和药物释放特性。Eudragit® E (EuE) 是一种基于甲基丙烯酸酯的阳离子共聚物，能够为局部应用生产出柔韧且具有粘性的薄膜。在这项研究中，全面评估了增塑剂对基于 EuE 的贴剂的机械性能、粘性和 5-FU 释放特性的影响。虽然随着三醋酸甘油酯 (triacetin)、癸二酸二丁酯 (DBS) 和柠檬酸三乙酯 (TEC) 浓度的增加，薄膜的断裂伸长率（%）和附着力显著增加，但拉伸强度呈反比关系。用 40%三醋酸甘油酯、30% DBS 或 40% w/w TEC 增塑的 EuE 可产生最适合局部应用的弹性和粘性薄膜。载有 5-FU 的贴剂的体外释放研究表明，在最初的 10 分钟内出现初始突释模式，随后在 120 分钟内缓慢释放。总之，这项研究为制备具有所需机械性能、粘性和 5-FU 释放特性的基于 EuE 的贴剂提供了重要信息，这可能使其在治疗 NMSC 方面具有潜在的应用。
