Polymer-Based Approaches for Exploring Polymorph Space

基于聚合物的多晶型空间探索方法

• 批准号: 7426730
• 负责人: Adam Jay Matzger
• 金额: $ 5.21万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7426730
• 关键词: Address; Azithromycin; Behavior; Bioavailable; Biological Availability; Characteristics; Chemicals; Computer Simulation; Constitution; Controlled Study; Crystallization; Depth; Development; Drug Delivery Systems; Drug Formulations; Effectiveness; Equilibrium; Event; Flutamide; Future; Ganciclovir; Goals; Growth; Isomerism; Itraconazole; Ketoconazole; Kinetics; Lead; Libraries; Methodology; Methods; Numbers; Outcome; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Polymers; Production; Property; Public Health; Rate; Research; Research Personnel; Role; Solid; Solubility; Spectrum Analysis; Staging; Structure; Surface; Techniques; Testing; Therapeutic Agents; aqueous; base; dehydroepiandrosterone; density; design; dosage; functional group; method development; molecular recognition; neutrophil; novel; programs; solid state

The role of solid-state form in determining the properties of Pharmaceuticals is a critical issue in drug delivery. The ability of a solid to exist as more than one polymorph, supramolecular isomers that differ only in packing and not constitution, creates a situation where each crystal form may have different bioavailability and stability. Only by discovering the presence of new polymorphs and their unique properties can the most efficacious form for a solid dosage be found. This proposal outlines a method for studying and controlling this important aspect of crystal growth. Specific Aim 1-Develop a general methodology for producing new polymorphs. We will create libraries of polymers that can heteronucleate crystallization of solids. It is proposed that varying the functional groups on the surface of the polymer and the orientation and density of these functional groups will allow kinetic access to new polymorphs by creating novel heteronucleation events. Specific Aim 2-lnvestigate the relationship between polymer structure and crystal polymorph obtained. Though it has been established that the majority of crystallizations on a macroscopic scale proceed through heteronucleation events, there is little information about the influence of the substrate on crystallization events. Using the approach developed in Specific Aim 1 to find polymers that create novel polymorphs, we will determine which characteristics are important for controlling polymorph production. Specific Aim 3-Determine the properties of novel polymorphs. With the ultimate goal of finding more efficacious forms of existing and new Pharmaceuticals, the determination of several key properties of the new polymorphs will be undertaken including stability, equilibrium solubility and dissolution rate. brief description of public health relevance: The effectiveness of a drug substance is not solely related to its chemical composition but also to how the molecules arrange in the solid. This proposal offers a method for optimizing this important aspect of drug delivery and will lead to the development of more effective forms of current and future therapeutic agents.

固态形式在确定药物特性中的作用是药物的关键问题 送货。固体存在的能力是多种多晶型，超分子异构体的能力 在包装而不是宪法中，创建每种水晶形式可能具有不同生物利用度的情况 和稳定性。只有发现新的多晶型物及其独特的特性才能最大 可以找到固体剂量的有效形式。该建议概述了研究和控制的方法 晶体生长的这一重要方面。 特定的目标1开发一种用于产生新多晶型物的一般方法。我们将创建库 可以异核核结晶的聚合物。建议改变官能团 在聚合物的表面以及这些官能团的方向和密度将允许动力学 通过创建新型的异核事件来访问新的多晶型物。 特定的AIM 2-LNVEST，可以在获得的聚合物结构与获得的晶体多晶之间的关系。 尽管已经确定宏观量表上的大多数结晶一直通过 杂核事件，关于底物对结晶的影响的信息很少 事件。使用特定目标1中开发的方法来查找产生新型多晶型物的聚合物，我们 将确定哪些特征对于控制多晶型物的生产很重要。 特定目标3确定性新型多晶型物的特性。最终目标是找到更多 有效形式的现有药物和新药，确定了几种关键特性 将进行新的多晶型物，包括稳定性，平衡溶解度和溶解速率。 公共卫生相关性的简要说明： 药物的有效性与其化学成分不仅与 分子排列在固体中。该建议提供了一种优化药物这一重要方面的方法 交付，并将导致开发更有效的当前和未来治疗剂的形式。