Dosage Form Design Strategies for Delivery of UC781 and Tenofovir

杀微生物剂产品的开发已成为艾滋病毒预防领域的一个重要焦点。这些产品 在性交前应用以防止感染艾滋病毒有可能成为一线 在抗击艾滋病毒传播方面的防御。然而，可接受的杀微生物剂候选配方如下 如果此方法要成功，则需要。尽管一些潜在的杀微生物剂候选药物 虽然已经确定，但对产品配方的关注很少。逆转录酶抑制剂 替诺福韦(TFV)和UC781具有显著的抗HIV活性。尽管目前凝胶阴道产品 在临床上对这些候选药物进行评估，最终可能有必要开发多剂量 平台为用户提供他们可以在其社交网络的限制内随时使用的产品 环境、个人选择和环境条件。在这个节目中，快速溶解阴道膜 将为TFV、UC781以及两者的组合开发。薄膜剂型很容易使用，是 制造成本低，易于运输，不再需要产品涂抹器。这 该项目还解决了UC781的配方问题，该问题影响到所有剂型。UC781拥有 极低的水溶解度，并经历氧化降解。这一属性使表述变得困难。 在这个项目中，使用络合和共结晶作为增溶和稳定的手段 将探索UC781。该化合物的成功增溶/稳定将为更多的 有效地将UC781并入剂型。最终由分散的薄膜和凝胶组成的面板 将对实施这些交付战略的配方和配方进行全面的产品评估 比较一下。最有希望的配方将被推进到猴子的安全性和有效性测试中 项目2，并最终通过核心C扩大规模，并在项目3和4中提前进行人体研究。 该项目还包括对熔融挤压使用的潜力进行评估，这提供了一些 从制造和经济角度受益，用于生产TFV和UC781薄膜产品。 将热熔融挤压制造技术与水溶液浇注技术进行比较。

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.