Aqueous-based Two-Step Spray Drying as a Taste Masking Drug Delivery Platform

总结 许多药物是苦的，克服这种苦味是开发成功的药物的主要障碍。 产品用于儿科患者。据报道，儿童的依从率低至11%，原因是 适口性/味道以及可吞咽性和剂量灵活性问题，所有这些都在本文中得到解决。 拟议项目。我们的总体目标是开发一种微米大小的、掩味的药物输送平台 对于可以容易地掺入各种适合的口服剂型的各种药物 用于儿科患者，包括混悬剂、口服溶解片剂、其他多颗粒系统， 和口腔可分散膜。这种广泛适用的掩味递送平台可用于 任何不太可口的化学实体，这可能有助于药物开发过程， 更可口的产品，以更快的速度和更低的成本到达儿科患者。我们提出了一个 新的两步喷雾干燥法制备密封微粒。喷雾干燥是常用的 在制药工业中用于制备掺入各种剂型的微粒。 然而，这些颗粒是基质，其中药物分布在整个颗粒中， 因此，当口服给药时，其可以与味蕾相互作用。因此，传统 喷雾干燥不能有效地掩盖味道，特别是对于强烈苦味的药物。拟议 项目，我们将准备传统的基质微粒，然后应用第二涂层， 药学上可接受的聚合物，其不溶于唾液但易溶于唾液中。 胃该第二涂层将在基质微粒的外表面上螯合药物 并阻止与味蕾的互动。此外，这些聚合物的pH依赖性溶解度将 允许喷雾干燥过程是完全水基的，因此我们避免使用有机溶剂。 溶剂以及与其使用相关的毒理学和环境问题。我们假设 密封的基质微粒将比常规的喷雾干燥基质更可口。后 表征微粒的尺寸、形态结构和在两种中的体外溶出度， 模拟唾液和胃液，我们将使用随机，双盲临床试验来测试我们的假设。 年龄分层的儿童口味小组的研究。儿童将评价配方的适口性 用的是七分面部快乐量表为拟议项目选择的两种模型苦味药物 对乙酰氨基酚（水溶性）和布洛芬（水溶性差）。这些是众所周知的苦 在儿科患者中常规安全使用的药物， 溶解度，以评估这种新的两步喷雾干燥技术作为掩味剂的适用性 用于可溶性和难溶性药物的平台。

Summary Many drugs are bitter and overcoming this bitter taste is a major barrier in developing a successful product for pediatric patients. Compliance rates as low as 11% have been reported in children due to palatability/taste as well as swallowability and dose flexibility issues, all of which are addressed in this proposed project. Our overall goal is to develop a micron-sized, taste masked drug delivery platform for a wide range of drugs that can be readily incorporated into a variety of oral dosage forms suitable for pediatric patients, including suspensions, orally dissolving tablets, other multiparticulate systems, and orodispersible films. Such a broadly applicable taste masking delivery platform could be used for any poorly palatable chemical entity, which could facilitate the drug development process, allowing more palatable products to reach pediatric patients more rapidly and at reduced costs. We propose a novel two-step spray drying process to prepare sealed microparticles. Spray drying is commonly used in the pharmaceutical industry to prepare microparticles for incorporation into various dosage forms. These particles, however, are matrices, where drug is distributed throughout the particle, including on the surface, which can thus interact with taste buds when administered orally. Therefore, conventional spray drying does not effectively mask taste, especially for aggressively bitter drugs. In the proposed project, we will prepare conventional matrix microparticles then apply a second coating using pharmaceutically acceptable polymers that are insoluble in the saliva but readily soluble in the stomach. This second coating will sequester drug on the exterior surface of the matrix microparticles and prevent interaction with taste buds. Moreover, the pH-dependent solubility of these polymers will allow the spray drying process to be completely aqueous-based and thus we avoid the use of organic solvents and the toxicological and environmental issues associated with their use. We hypothesize that sealed matrix microparticles will be more palatable than conventional spray dried matrices. After characterizing the microparticles for size, morphologic structure and in vitro dissolution in both simulated saliva and gastric fluid, we will test our hypothesis using a randomized, double blind clinical study with an age-stratified pediatric taste panel. Children will rate palatability of the formulations using a seven point facial hedonic scale. The two model bitter drugs selected for the proposed project are acetaminophen (water-soluble) and ibuprofen (poorly water-soluble). These are well-known bitter drugs that are routinely and safely used in pediatric patients and represent a range of aqueous solubilities to assess the applicability of this novel two-step spray drying technique as a taste masking platform for both soluble and poorly soluble drugs.