Dosage Form Design Strategies for Delivery of UC781 and Tenofovir

杀微生物剂产品开发已成为艾滋病毒预防领域的一个重要重点。这些产品 在性交前应用，以防止艾滋病毒感染，有可能成为第一道防线， 在抗击艾滋病毒传播方面的防御。然而，杀微生物剂候选物的可接受制剂是可接受的。 如果这种方法要取得成功，就需要。尽管许多潜在的杀微生物剂候选药物已经 虽然已经确定，但很少关注产品配方。逆转录酶抑制剂 替诺福韦（TFV）和UC 781具有显著的抗HIV活性。虽然凝胶阴道产品目前 在临床上对这些候选人进行评估，最终，可能需要开发多剂量 平台，为用户提供他们可以在社交网络的限制范围内随时使用的产品。 环境、个人选择和环境条件。在这个节目中，快速溶解阴道片 将为TFV、UC 781以及两者的组合开发。薄膜剂型易于应用， 制造成本低，易于运输，并且消除了对产品施用器的需要。这 项目还解决了UC 781的配方问题，该问题影响所有剂型类型。UC 781有 非常低的水溶性，并经历氧化降解。这一属性使公式化变得困难。 在该项目中，使用络合和共结晶作为增溶和稳定的手段， UC 781将被探索。该化合物的成功增溶/稳定化将为更多的研究提供基础。 将UC 781有效地掺入剂型中。最终形成一层分散的薄膜和凝胶 制剂和实施这些交付策略的制剂将在一个全面的产品中进行评估， 对比最有前途的制剂将在2010年进行猴子安全性和有效性测试。 项目2最终通过核心C扩大规模，并在项目3和4中进行人类研究。 该项目还包括评估使用熔融挤出的潜力， 从制造和经济的角度来看，用于生产TFV和UC 781薄膜产品。 将热熔挤出制造与水溶剂浇铸技术进行比较。

Microbicide product development has become an essential focus in the HIV prevention field. These products are applied prior to sexual intercourse to prevent HIV acquisition have the potential to become the first line of defense in combating the spread of HIV. However, acceptable formulations of microbicide candidates are required if this approach is to succeed. Although a number of potential microbicide drug candidates have been identified, little attention has been given to product formulation. The reverse transcriptase inhibitors tenofovir (TFV) and UC781 have significant activity against HIV. Although gel vaginal products are currently being evaluated in the clinic for these candidates, ultimately, it may be necessary to develop multiple dosage platforms to provide users with products that they can readily use within the constraints of their social environment, personal choice, and environmental conditions. In this program, quick dissolve vaginal films will be developed for TFV, UC781, and a combination ofthe two. Film dosage forms are easily applied, are inexpensively manufactured, are easily transportable, and eliminate the need for product applicators. This project also addresses a formulation issue with UC781 which impacts all dosage form types. UC781 has very low aqueous solubility and undergoes oxidative degradation. This attribute makes formulation difficult. In this project, the use of complexation and co-crystallization as a means for solubilization and stabilization of UC781 will be explored. Successful solubilization/stabilization ofthis compound will provide a basis for more efficient incorporation of UC781 into a dosage form. Ultimately a panel of dispersed film and gel formulations and formulations implementing these delivery strategies will be evaluated in a thorough product comparison. The most promising formulations will be advanced to monkey safety and efficacy testing in Project 2 and ultimately scaled up through Core C and brought forward to human studies in Projects 3 and 4. This project also includes evaluation of the potential for the use of melt extrusion which provides certain benefit from a manufacturing and economic standpoint, for the production of TFV and UC781 film products. Manufacture by hot melt extrusion will be compared with aqueous solvent casting technology.