Bioequivalence of Topical Products: Elucidating the Thermodynamic and Functional Characteristics of Compositionally Different Topical Formulations

摘要 仿制药的一般要求是，该产品是非专利的，含有活性成分， 先前批准的药物中的成分，并显示与先前批准的药物具有生物等效性 药控制皮肤外用药物效果的基本力量可以归纳为 在三个不同的维度上。1.活性药物成分（API）与 赋形剂（制剂因子、溶解度），2.皮肤接触API（热力学和药效学 活动）和3。赋形剂与皮肤接触（渗透增强、扩散性、刺激性）。一个深思熟虑 欣赏，然后是彻底的理解，然后是仔细的审议，可以帮助减轻一些 这三个方面可能产生的失败模式，并导致仿制药不被批准 应用.然而，有一个难以捉摸的第四维，心理流变学或感官/感知 决定最终结果的流变学性质（和其他感官性质）的判断 用户/消费者对产品的最终验收。通过这个项目，我们旨在开发有意义的风险 缓解方法及其科学依据。这些将包括考虑产品行为， 开发/制造的各个阶段，一直到观察变形产品 施加到皮肤上的治疗部位。仿制局部产品的开发一直是 受BE评估的昂贵临床试验和应用成本等因素的阻碍， 由于对申请的个案评估，一个繁琐的应用程序包是 通常需要的是在硬币的两面浪费宝贵的资源和时间。该项目将确保 迫切需要的理论和实践框架，可以使彻底而有效的评估， 局部通用产品应用。

Abstract The general requirements for generics to be considered are that the product is off-patent, contains an active ingredient in a previously approved medicine and is shown to be bioequivalent to that previously approved medicine. The fundamental forces governing the effects of topical drugs applied to the skin can be summed up in three distinct dimensions. 1. The interaction of the active pharmaceutical ingredient (API) with the excipients (formulation factors, solubility), 2. API with the skin (thermodynamic and pharmacodynamic activity) and 3. Excipient with the skin (penetration enhancement, diffusivity, irritancy). A thoughtful appreciation followed by a thorough understanding and then careful deliberations can help mitigate a number of failure modes that can arise from these three dimensions and result in disapproval of generic drug applications. However, there is an elusive fourth dimension, the psychorheology or the sensory/perceptive judgement of the rheological properties (and other organoleptic properties) that dictates the end user/consumers final acceptance of the product. Through this project we aim to develop meaningful risk mitigating methods and their scientific basis. These will encompass considering product behaviour during various stages of development/manufacturing, all the way to looking at the metamorphosing product as it is being applied to the treatment site on the skin. The development of generic topical products has been hampered by factors such as expensive clinical trials for BE assessment and application costs which get blown out due to the case by case assessment of applications. A burdensome application package is generally needed that wastes valuable resources and time on both sides of the coin. This project will ensure the much needed theoretical and practical framework that can enable a thorough yet efficient assessment of topical generic product applications.