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

优化的口服吸入药物溶出度测试系统：开发与应用

• 批准号: 8904332
• 负责人: Guenther Hochhaus
• 金额: $ 4.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 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 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8904332
• 关键词: Optimized; Dissolution; Test; System; Orally

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.

项目摘要/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 在没有进行研究的情况下，新药或药物配方在患者身上的行为 在人类或动物身上。本研究有兴趣开发和验证一种体外 预测口服吸入性药物(OIDP)微粒溶出度的测定方法 从而能够预测吸入药物的体内行为 制剂，因为它涉及药物/制剂性能之间的相互关系， 药物在肺衬里液体中的溶解和对肺的影响 吸收，全身副作用。建议的研究可分为三个部分： 首先，建议的溶解装置将根据溶解情况进行优化 所使用的介质(需要一种反映肺部状况的溶解介质)， 检测装置的用药量和给药机理，总体设计 溶解装置等因素。在对系统进行优化后，第二部分 这项研究将评估一系列商业化和试验性药物。 在物理化学性质、传递方式(计量吸入器、 干粉吸入器雾化器)、制剂(溶液、粉剂、悬浮剂)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，文献中介绍的药代动力学研究将是 年口服避孕药进入全身循环的比率分析 人类。这些数据与溶出度测试中产生的数据相关 实验。它的目的是在体外溶出之间提供一种强有力的联系 OIDPs的数据和体内吸收特性。