Development of hydrogel-based in vitro dissolution apparatus for microparticle formulations

项目总结 开发药物配方是为了使药物最大限度地造福于患者。最大值 当药物以预定的方式正确释放时，患者就会受益 最低有效浓度和最高中毒浓度之间的剂量，治疗剂量 射程。使用药物溶出性进行质量控制的基本假设是不同的 只要体外释药，制剂有望具有相同的体内药物吸收性能 动力学也是一样的。然而，对于非专利制剂，类似的体外溶出性不同 保证它们在体内具有相同的吸收特性。这很简单，因为体外培养 溶解性能取决于所使用的溶解方法。关于使用体外溶出性的问题 作为一种比较不同配方的手段，对于非口服配方来说变得复杂，例如 缓释(SR)注射用仓库制剂。在众多的肠外仓库配方中， 微粒制剂是最常用的制剂，也是本研究的重点。 本项目的目标是设计和开发新的体外溶出装置，该装置可以 体内性质，即制剂在注射后可能遇到的条件。确实有 三个具体目标。这三个目标将同时实现，因为它们是相互依存的。第一 具体目的是设计和开发用于检查肠外SR的新型体外溶出仪 配方。为方便起见，这些设备将被设计成与现有的USP设备类型4相结合 与现有测试设备的适应性。第二个具体目标是制备SR曲普瑞林 使用微细加工方法制备微粒，并与现有的临床产品进行比较。 这将是Aina的新的基于水凝胶模板的微制造方法和 传统的双乳技术以及商业上可用的曲普瑞林的特瑞星� 用作对照制剂的微粒。第三个具体目标是进行体外溶出 对制备的制剂进行研究，确定最灵敏的溶出度方法。方剂 在第二个目标中准备的材料将通过作为第一个目标的一部分制定的方法进行测试，以便确定 一种溶出法，用于区分SR制剂之间的差异。 区分SR配方中的差异的能力与物理化学特性一样重要 与制剂相关的差异可能会影响药物的生物利用度。圆满完成 该项目预计将生产一种新的溶出仪，有助于区分配方 在不同的制造条件下产生。这种溶出度测定将通过以下方式帮助整体公众健康 提高能力，确保所有注射用SR制剂具有适当的生物利用度和 持续治疗剂量的释放曲线。

PROJECT SUMMARY Drug formulations are developed to deliver drugs for the maximum benefit to patients. The maximum benefit to the patients occurs when the drug is released correctly in a predetermined manner to maintain the dose between the minimum effective concentration and upper level toxic concentration, the therapeutic dose range. The underlying assumption of using the drug dissolution property for quality control is that different formulations are expected to have the same in vivo drug absorption property as long as the in vitro drug release kinetics are the same. For generic formulations, however, the similar in vitro dissolution property does not guarantee that they would have the same in vivo absorption properties. This is simply because the in vitro dissolution property depends on the dissolution method used. The issue of using in vitro dissolution property as a means to compare different formulations becomes complicated for non-oral formulations such as sustained release (SR) parenteral depot formulations. Of the many parenteral depot formulations, microparticle formulations have been most frequently used and are the focus of this study. The goal of this project is to design and develop new in vitro dissolution apparatus that can incorporate in vivo properties, i.e., conditions that a formulation may encounter after parenteral administration. There are three specific aims. The three aims will be conducted simultaneously, as they are interdependent. The first specific aim is to design and develop new in vitro dissolution apparatuses for testing parenteral SR formulations. These apparatus will be designed to incorporate into the existing USP apparatus type 4 for ease of adaptation with current testing equipment. The second specific aim is to formulate SR triptorelin microparticles using microfabrication method and compare these with the currently existing clinical product. The comparison will be between Akina's novel hydrogel-template based microfabrication method and conventional double emulsion technique as well as with Trelstar�, which is a commercially available triptorelin microparticle to be used as a control formulation. The third specific aim is to conduct in vitro dissolution studies of the prepared formulations and identify the most sensitive dissolution method. The formulations prepared in the second Aim will be tested by the methods developed as part of the first aim in order to identify a dissolution method which discriminates the differences between the SR formulations. The ability to distinguish differences in SR formulations is important as the physicochemical differences relevant to the formulation may affect the bioavailablity of the drug. The successful completion of this project is expected to produce a new dissolution apparatus which can aid in distinguishing formulations generated under different manufacturing conditions. This dissolution assay will aid overall public health by improving the capability to ensure that all injectable SR formulations have the appropriate bioavailability and release profiles for sustained therapeutic dose.