Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany; Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Int J Pharm. 2020 Feb 15;575:118886. doi: 10.1016/j.ijpharm.2019.118886. Epub 2019 Nov 29.
Drug crystallization in transdermal patches is still a major challenge, confronting the formulation development of topical drug delivery systems. Encapsulation of drugs into nanoparticles is proposed here as a promising tool for regulating drug crystallization in transdermal patches. The degree of recrystallization and transdermal permeation of ibuprofen and hydrocortisone loaded in polymeric and lipid nanoparticles from matrix-type transdermal patches were investigated. Ethyl cellulose (EC4), poly (lactide-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were employed for polymeric nanoparticle preparations; while medium chain triglyceride (MCT) and witepsol were used for the preparation of MCT nanoemulsion and solid lipid nanoparticles (SLNs), respectively. As control, similar patches were prepared containing the free form of the investigated model drugs. All nanoparticle-containing transdermal patches exhibited less degree of drug recrystallization after 4 weeks compared to the control groups. Among the investigated nanocarriers, transdermal patches formulated with drug-loaded lipid nanoparticles showed the lowermost degree of recrystallization. Drug encapsulation into SLNs succeeded to reduce the degree of ibuprofen and hydrocortisone recrystallization from 23.3 ± 0.9 and 21.9 ± 1.2% to 0.2 ± 0.1 and 1.8 ± 0.1%, respectively. Additionally, the decreased crystalline fraction was accompanied by a corresponding increase in the drug flux through excised pig skin, which was found to be correlated to the hydrophobicity of the different nanocarriers. In conclusion, polymeric and lipid nanoparticles proved to be effective tools for the preparation of transdermal patches with on-demand drug loadings, while lowering the recrystallization risks. Moreover, the results of this study can be a valuable guidance for the design of effective transdermal patches by controlling the crystallization of various drugs through fine tuning of the carrier hydrophobicity.
药物在透皮贴剂中的结晶仍然是一个主要挑战，这给局部药物传递系统的制剂开发带来了困难。本文提出将药物包封成纳米颗粒作为一种有前途的工具，用于调节透皮贴剂中药物的结晶。研究了载有布洛芬和氢化可的松的聚合物和脂质纳米颗粒在基质型透皮贴剂中的再结晶程度和透皮渗透。采用乙基纤维素（EC4）、聚（乳酸-共-乙醇酸）（PLGA）和聚己内酯（PCL）制备聚合物纳米颗粒；而中链甘油三酯（MCT）和 Witepsol 分别用于制备 MCT 纳米乳和固体脂质纳米粒（SLN）。作为对照，制备了含有研究模型药物游离形式的类似贴剂。与对照组相比，所有含纳米颗粒的透皮贴剂在 4 周后显示出较低的药物再结晶程度。在所研究的纳米载体中，载药脂质纳米粒的透皮贴剂表现出最低的再结晶程度。将药物包封到 SLN 中成功地将布洛芬和氢化可的松的再结晶程度从 23.3±0.9%和 21.9±1.2%分别降低至 0.2±0.1%和 1.8±0.1%。此外，结晶分数的减少伴随着药物通量通过离体猪皮的相应增加，这与不同纳米载体的疏水性有关。总之，聚合物和脂质纳米粒被证明是制备具有按需药物负载的透皮贴剂的有效工具，同时降低了再结晶风险。此外，本研究的结果可以为通过精细调节载体疏水性控制各种药物的结晶来设计有效的透皮贴剂提供有价值的指导。
