Bhattaccharjee Sonalika Arup, Kale Madhura, Le Ngan, Banga Ajay K
Center for Drug Delivery Research, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 3001 Mercer University Dr, Atlanta, Georgia, 30341, USA.
Oglethorpe University, Atlanta, Georgia, USA.
AAPS PharmSciTech. 2021 May 10;22(4):150. doi: 10.1208/s12249-021-02022-w.
Suspension-based matrix transdermal delivery systems (TDSs) are specialized systems that maintain a continuous driving force for drug delivery over prolonged wear. The pressure-sensitive adhesive (PSA) is the most critical constituent of such systems. Our study aimed to determine the effect of different mixing methods on the performance of silicone PSA-based suspension TDSs. Lidocaine suspension TDSs were prepared using conventional slow rotary mixing, high-speed homogenization, bead-mill homogenization, vortex shaking, and by an unguator. Resultant TDSs were tested for tack, shear, and peel properties and correlated to coat weight, content uniformity, microstructure, and in vitro permeation across dermatomed human skin. Every mixing method tested caused a significant reduction in peel. However, bead-mill homogenization resulted in significant loss of all adhesive properties tested, while unguator-mixed TDSs retained most properties. Good linear correlation (R = 1.000) between the shear properties of the TDSs with the average cumulative amount of lidocaine permeated after 24 h was observed, with no significant difference between percutaneous delivery from slow rotary-mixed systems (1334 ± 59.21 μg/cm) and unguator-mixed systems (1147 ± 108.3 μg/cm). However, significantly lower delivery from bead-mill homogenized systems (821.1 ± 28.00 μg/cm) was noted. While many factors affect TDS performance, careful consideration must also be given to the processing parameters during development as they have been shown to affect the resultant system's therapeutic efficacy. Extensive mixing with bead-mill homogenization demonstrated crystallization of drug, loss in adhesive properties, coat weight, and film thickness, with reduced transdermal delivery of lidocaine from the prepared system.
基于混悬液的基质透皮给药系统（TDS）是一种特殊的系统，在长时间佩戴过程中能维持持续的药物递送驱动力。压敏胶（PSA）是此类系统中最关键的成分。我们的研究旨在确定不同混合方法对基于有机硅PSA的混悬液TDS性能的影响。使用传统的慢速旋转混合、高速均质化、珠磨均质化、涡旋振荡以及通过一种软膏搅拌机来制备利多卡因混悬液TDS。对所得的TDS进行粘性、剪切力和剥离性能测试，并与涂层重量、含量均匀度、微观结构以及在离体人皮肤上的体外渗透情况相关联。所测试的每种混合方法都会导致剥离力显著降低。然而，珠磨均质化导致所有测试的粘附性能显著丧失，而通过软膏搅拌机混合的TDS保留了大部分性能。观察到TDS的剪切性能与24小时后利多卡因渗透的平均累积量之间具有良好的线性相关性（R = 1.000），慢速旋转混合系统（1334 ± 59.21 μg/cm）和软膏搅拌机混合系统（1147 ± 108.3 μg/cm）的经皮给药量之间无显著差异。然而，注意到珠磨均质化系统的给药量显著更低（821.1 ± 28.00 μg/cm）。虽然许多因素会影响TDS性能，但在研发过程中也必须仔细考虑加工参数，因为已证明它们会影响所得系统的治疗效果。通过珠磨均质化进行广泛混合显示出药物结晶、粘附性能、涂层重量和膜厚度的损失，以及所制备系统中利多卡因的透皮给药减少。
