Tiered Testing Strategy for Assessing Thermal Effects on Transdermal Products

评估透皮产品热效应的分层测试策略

• 批准号: 8692359
• 负责人: Kevin S. Li
• 金额: $ 49.44万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8692359
• 关键词: Tiered; Testing; Strategy; Assessing; Thermal

Many transdermal systems are affected by temperature and are labeled with a warning against heat application. For example, heat can increase skin permeability. Heat can affect drug solubility in a formulation and drug (and excipient) release from the transdermal system. Heat can also increase dermal clearance and systemic drug absorption via the vascular network. Heat effects can be different among different transdermal delivery systems. In the FDA review process, when the reference product has a label warning against heat application, the generic product cannot be more sensitive to heat than the reference product. Different heat effects among transdermal products can be due to different drug release (and formulation release) from the products. In addition, due to the different formulation release under heat, these formulations can exert different effects on skin permeability. The different formulation release and penetration into the dermis can also affect dermal clearance for systemic drug absorption. The objectives of this project are to (a) investigate the in vitro release test conditions for identifying heat effects on transdermal delivery and (b) develop an in vitro test process to be used in the reviews of transdermal products to ensure that generic products do not introduce any additional safety risks. We will evaluate the influence of heat upon the rate of drug release from the patch using in vitro release testing of USP dissolution apparatus (tier 1), drug and formulation permeation across skin using Franz diffusion cells (tier 2), and dermal clearance analyses using an existing, state-of-the-art, skin diffusion model to determine dermis concentration and drug absorption into the vascular network in the dermis (tier 3). It is hypothesize that this tiered in vitro testing strategy will yield a scientifically-based decision tree to support the evaluation of thermal effects for ANDA approvals of transdermal products.

许多透皮系统都会受到温度的影响，并贴有高温警告标签 应用。例如，热量可以增加皮肤的渗透性。热量会影响药物在制剂中的溶解度 以及药物（和赋形剂）从透皮系统的释放。热量还可以增加真皮间隙 通过血管网络进行全身药物吸收。不同透皮方式的热效应可能不同 输送系统。在 FDA 审查过程中，当参考产品有防热标签警告时 应用中，通用产品不能比参考产品对热更敏感。热量不同 透皮产品之间的影响可能是由于不同的药物释放（和制剂释放） 产品。此外，由于制剂在热下的释放不同，这些制剂可以发挥不同的作用。 对皮肤渗透性的影响。不同的制剂释放和对真皮的渗透也会影响 皮肤清除以促进全身药物吸收。该项目的目标是 (a) 研究体外 发布用于识别热对透皮递送影响的测试条件，并 (b) 开发体外测试 用于审查透皮产品的流程，以确保仿制药不会引入任何 额外的安全风险。我们将评估热量对贴剂药物释放速率的影响 使用 USP 溶出度仪（第 1 级）进行体外释放测试，药物和制剂在皮肤上的渗透 使用 Franz 扩散池（第 2 层），并使用现有的最先进的皮肤进行皮肤清除分析 扩散模型确定真皮浓度和药物吸收到真皮血管网络中 （第 3 级）。假设这种分层体外测试策略将产生一个基于科学的决策树 支持透皮产品 ANDA 批准的热效应评估。