Engineering Microparticles for Taste-Masking and Controlled Release of Pediatric

描述(由申请人提供)：儿科药物开发在有效治疗儿童疾病方面提出了许多独特的挑战，从充足的剂量信息和儿科专用测试到可口的风味特征和有效的给药形式。一本小说 在剂量设计和格式上提供灵活性的同时掩盖苦味药物味道的技术，将使现有的成人药物产品能够配制成专门为儿科患者设计的药物。我们建议的策略使用精密颗粒制造(PPF)来开发儿科药物载药微粒，以掩盖苦味并允许灵活的剂量和格式。PPF技术的核心优势在于其对颗粒大小、形状、材料和释放速率的精确控制。我们的长期目标是采用这种灵活、用户友好、廉价的技术来创建一个微囊化难吃的儿科活性药物成分(API)的平台。我们假设，由PPF生产的均匀、精确的工程微粒将有效地为儿科药物创造味道掩蔽的配方，同时还允许在消化条件下快速和受控地释放活性物质。我们进一步假设，这一强大的微粒战略将允许准确、灵活的剂量和适应多种药物输送形式。我们的研究团队将开发和表征含有苦味原料药的模型微粒，这些微粒具有精确控制的物理化学特征，旨在满足适口性标准(目标1)。然后，我们将优化这些模型微粒的释放特性和掩盖味道的性能(目标2)。其结果将是模型载药微粒，符合基于颗粒大小、均匀性和药物表面浓度的适口性标准，并可根据所需的消化条件下的释放曲线进行定制。在确定了精确设计这些微粒的可行性后，第二阶段将专注于味道和口感的感官特性的临床评估，以及剂量准确性、滴定和格式灵活性的演示。这种基于PPF的封装策略解决了儿科药物的适口性、剂量准确性和格式灵活性问题，同时改进了现有的封装技术，这些技术昂贵且耗时，并产生控制不佳的不同批次的微粒。此外，该PF技术对多种药物和基质/包衣材料以及规模化生产具有很强的适应性。其结果将是一个廉价、高度灵活的儿科平台，用于创建美味、适合年龄和准确的剂型，导致更安全的儿科配方和改善患者的依从性。 与公共卫生相关：由于依从性差、临时配方和危险的用药错误，儿科药物配方不足影响了对儿童疾病的有效治疗。问题的基础是适口性、准确的剂量和适合年龄的剂量格式挑战。需要开发一种用户友好、廉价的开发平台，用于现有成人药物产品的儿科重新配方，以管理具有控制释放速率的味道遮盖的活性药物成分(API)。该项目使用模型BATHER原料药，旨在测试精密颗粒制造技术生产适口、适龄和准确剂量的可行性，作为一种更安全的儿科用药和更好的依从性的手段。

DESCRIPTION (provided by applicant): Pediatric drug development presents many unique challenges in the effective treatment of diseases in children, from adequate dosing information and pediatric-specific testing to palatable flavor profiles and effective delivery formats. A novel technology that masks bitter drug flavors while providing flexibility in dose design and format would enable formulation of existing adult pharmaceutical products into medications specially designed for pediatric patients. Our proposed strategy uses Precision Particle Fabrication (PPF) to develop pediatric drug-loaded microparticles that mask bitter flavors and allow for flexible dosing and formats. The central advantage of PPF technology lies in its precise control of particle size, shape, material, and release rates. Our long-term goal is to adapt this flexible, user-friendly, inexpensive technology to create a platform for microencapsulating unpalatable pediatric active pharmaceutical ingredients (API's). We hypothesize that the uniform, precisely engineered microparticles produced by PPF will create effectively taste- masked formulations for pediatric drugs while also allowing for the swift and controlled release of the active agents under digestive conditions. We further hypothesize that this robust microparticle strategy will allow for accurate, flexible dosing and adaptation to multiple drug delivery formats. Our research team will develop and characterize model bitter API-containing microparticles with precisely controlled physicochemical features that are designed to meet palatability standards (Aim 1). We will then optimize the release characteristics and taste-masking performance of these model microparticles (Aim 2). The result will be model drug-loaded microparticles that meet palatability standards based on particle size, homogeneity, and drug surface concentration and that can be tailored for desired release profiles under digestive conditions. After establishing the feasibility of precisely engineering these microparticles, Phase II will focus on the clinical evaluation of organoleptic properties of taste and mouth feel as well as demonstration of dosing accuracy, titration, and format flexibility. This PPF-based encapsulation strategy addresses issues of palatability, dosage accuracy, and format flexibility in pediatric drugs, while improving upon existing encapsulation techniques that are costly and time-consuming and produce poorly controlled, heterogeneous batches of microparticles. In adition, this PF technology is highly adaptable to multiple drugs and matrix/coating materials as well as large-scale production. The result will be an inexpensive, highly flexible pediatric platform for creating palatable, age-appropriate, and accurate dosage forms, leading to safer pediatric formulations and improved patient compliance. PUBLIC HEALTH RELEVANCE: Inadequate pediatric pharmaceutical formulations impair effective treatment of diseases in children due to poor compliance, ad hoc formulations, and dangerous medication errors. At the foundation of the problem are palatability, accurate dosing, and age-appropriate dosage format challenges. Development of a user-friendly, inexpensive development platform for pediatric reformulation of existing adult drug products to administer taste-masked active pharmaceutical ingredients (APIs) with controlled release rates is needed. Using model bitter APIs, this project aims to test the feasibility of Precision Particle Fabricatio technology to produce palatable, age-appropriate, and accurate doses as a means to safer pediatric medications and better compliance.