An Optimized Dissolution Test System for Orally Inhaled Drugs: Development and Va

项目总结/摘要 体外分析是药物开发的重要组成部分，因为它们通常可以预测 新药或药物制剂在未进行研究的患者中的行为 在人类或动物身上。本研究旨在开发和验证体外 预测经口吸入制剂（OIDP）微粒溶出速率的试验 从而允许预测吸入药物的体内行为 制剂因为它涉及药物/制剂性质之间的相互关系， 药物在肺衬里液中的溶解和肺效应， 吸收，全身副作用。拟议的研究可分为三个部分： 首先，所提出的溶出装置将在溶出度方面进行优化。 使用的介质（需要反映肺中状况的溶出介质）， 药物量和药物施加到测试装置的机制，总体设计 溶解装置等因素。系统优化后，第二部分 这项研究将评估各种市售药物和试验药物 在物理化学性质、递送（定量吸入器， 干粉吸入器雾化器）、制剂（溶液、粉末、悬浮液）和 药物化合物的物理化学性质（亲水性、亲脂性....）。在 拟议工作的第三步，文献中的药代动力学研究将 分析了OIDP进入体循环的速率， 人类然后将这些数据与溶出试验中生成的数据相关 实验其旨在提供体外溶出度与 数据和OIDP的体内吸收特性。

Project Summary/Abstract In vitro assays are an important part in drug development, as they often allow prediction of the behavior of a new drug or drug formulation in patients without performing studies in humans or animals. This study is interested in developing and validating an in vitro assay that predicts the dissolution rate of particles of orally inhaled drug products (OIDP) in the lung, thereby allowing predictions of the in vivo behavior of inhaled drug formulations as it relates to the interrelationship between drug/formulation properties, dissolution of drug in the pulmonary lining fluid and the pulmonary effects and, after absorption, systemic side effects. The proposed study can be divided into three parts: First, the proposed dissolution device will be optimized with respect to the dissolution medium to be used (a dissolution medium reflecting the conditions in the lung is desired), drug amount and mechanism of applying drug to testing device , design of the overall dissolution device and other factors. After optimization of the system, the second part of the study will assess a wide range of commercially available and experimental drug formulations that differ in physicochemical properties, delivery (metered dose inhaler, dry powder inhaler nebulizer), formulation (solution, powder, suspension) and physicochemical properties of the drug compound (hydrophilic, lipophilic....). In the third step of the proposed work, pharmacokinetic studies present in the literature will be analyzed with respect to the rate with which OIDPs enter the systemic circulations in humans. These data are than correlated to data generated within the dissolution test experiments. It is intended to provide a strong relationship between in vitro dissolution data and in vivo absorption properties of OIDPs.