Studies on optimization of the bioavailability of poor water-soluble drugs

难溶性药物生物利用度优化研究

• 批准号: 253094535
• 负责人: Privatdozentin Dr. Monika Johannsen
• 金额: --
• 依托单位: Institut für Technische Thermodynamik und Kältetechnik (ITTK)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/253094535?language=en
• 关键词: Studies; optimization; bioavailability; poor; water

Highly effective, specific drugs are often chiral compounds with one or more chiral centers. Since new pharmaceutical products should contain only the active enantiomer, non-active or even contradictory effective enantiomers are considered as contamination of the product. In addition, such compounds are often poor and slowly soluble in aqueous media. Such drugs are characterized by a low bioavailability since the poor water-solubility and therewith low dissolution rate is a limiting step for their absorption and biological availability.Therefore, the aim of this project is to develop methods for selective separation of the biologically active enantiomer from the racemate solution directly combined with its formulation as submicron drug in a suitable porous carrier. Alternatively, the extraction of the active enantiomer will be investigated using appropriate adsorbents. For both concepts, the bioavailability of the active ingredients is studied and evaluated by pH depended and thus targeted release.The selective enrichment of the active enantiomer covers the selection and modification of suitable carrier materials and their adaptation to the specific requirements for adsorption and separation. The carrier materials which will be used are on one hand commercial chiral adsorbents such as cyclodextrins and cyclofructanes. On the other hand inorganic carrier based on achiral silica gels and AlO(OH) will be used, which for surface modification will be further derivatised with biocompatible chiral selectors. Amino acids or chiral alcohols, which will be fixed by chemical bonds on the particle surfaces, are intended to serve as chiral selectors. A suitable characterization, e.g. studies on particle size and morphology, will help to make a selection of promising carrier systems for the separation of enantiomers. The intended systematic investigations will enable the identification of optimal process conditions and a deeper insight into the relationship between process conditions and product properties such as an optimized dissolution behavior.

高效的特定药物通常是一个或多个手性中心的手性化合物。由于新的药物产品应仅包含活性对映异构体，因此非活性甚至矛盾的有效映异构体被视为产品的污染。此外，这种化合物通常很差，并且在水性培养基中缓慢溶。此类药物的特征是生物利用度较低，因为较差的水溶性和低溶解速率是它们吸收和生物可用性的限制步骤。因此，该项目的目的是开发方法，将生物活性型物种从Racemate溶液中选择性分离，将其与Racemate解决方案直接结合起来，将其与合适的配方中的配方构成合适的crarsirer carriers。或者，将使用适当的吸附剂研究活动对映异构体的提取。对于这两个概念，通过pH依赖并因此释放了活性成分的生物利用度。主动对映异构体的选择性富集涵盖了适当的载体材料的选择和修饰，及其适应了对吸附和分离的特定要求。将使用的载体材料一方面是商业手性吸附剂，例如环糊精和环形荷兰。另一方面，将使用基于Achiral Silica凝胶和ALO（OH）的无机载体，用于表面修饰，将通过生物相容性的手性选择器进一步衍生。氨基酸或手性醇（通过颗粒表面上的化学键将固定）旨在用作手性选择器。合适的表征，例如粒度和形态学的研究将有助于选择有前途的载体系统，以分离对映异构体。预期的系统研究将使鉴定最佳过程条件，并更深入地了解过程条件和产品属性（例如优化的溶解行为）之间的关系。