Engineering Microparticles for Taste-Masking and Controlled Release of Pediatric

用于儿科药物掩味和控释的工程微粒

• 批准号: 8396082
• 负责人: Cory Berkland
• 金额: $ 21.6万
• 依托单位: ORBIS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8396082
• 关键词: Address; Adult; Age; Biocompatible Coated Materials; Biological Assay; Caliber; Chairperson; Characteristics; Child; Childhood; Cities; Clinical; Development; Disease; Dosage Forms; Dose; Drug Delivery Systems; Drug Formulations; Drug Industry; Encapsulated; Engineering; Ensure; Evaluation; Feasibility Studies; Flavoring; Foundations; Goals; Hospitals; Incentives; Industry; Kansas; Masks; Medical Research; Medication Errors; Missouri; Modeling; Oral cavity; Particle Size; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Physician Executives; Positioning Attribute; Principal Investigator; Production; Property; Proteins; Provider; Research; Shapes; Solutions; Surface; Tablets; Taste Perception; Techniques; Technology; Testing; Thick; Time; Titrations; Universities; Work; base; capsule; compliance behavior; controlled release; design; dosage; drug development; effective therapy; experience; flexibility; improved; large scale production; meetings; new technology; particle; pediatric pharmacology; research clinical testing; segregation; success; technology development; user-friendly

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.

描述（由申请人提供）：小儿药物开发在有效治疗儿童疾病的有效治疗中提出了许多独特的挑战，从足够的给药信息和特定于儿科特定的测试到可口的风味概况和有效的递送格式。小说 在提供剂量设计和格式灵活性同时掩盖苦味药物的技术将使现有的成人药品制定成专门为儿科患者设计的药物。我们提出的策略使用精确的颗粒制造（PPF）开发了掩盖苦味味道并允许柔性给药和格式的小儿药物的微粒。 PPF技术的核心优势在于其对粒径，形状，材料和释放速率的精确控制。我们的长期目标是调整这种灵活，用户友好，廉价的技术，以创建一个平台，用于微封装不可能的儿科活性药物（API）。我们假设由PPF生产的统一，精确设计的微粒将为小儿药物提供有效的味觉掩盖配方，同时还允许在消化条件下快速而受控的活性剂释放。我们进一步假设，这种鲁棒的微粒策略将允许准确，柔性剂量并适应多种药物递送格式。 我们的研究团队将开发并表征具有精确控制的物理化学特征的模型含API的微粒，旨在符合可口标准（AIM 1）。然后，我们将优化这些模型微粒的释放特性和味觉掩盖性能（AIM 2）。结果将是基于粒径，均匀性和药物表面浓度符合适口性标准的药物加载的微粒，并且可以在消化条件下针对所需的释放曲线量身定制。在确定这些微粒的可行性之后，第二阶段将重点介绍对味道和口腔感觉的有机精神特性的临床评估，并证明了给药精度，滴定和格式的灵活性。这种基于PPF的封装策略解决了小儿药物的可口性，剂量准确性和格式灵活性的问题，同时改善了现有的封装技术，这些技术既昂贵又耗时，并产生了不良控制的，异质批量的微颗粒。在ADITION中，该PF技术高度适应多种药物和基质/涂料材料以及大规模生产。结果将是一个廉价，高度灵活的儿科平台，用于创建可口，适合年龄和准确的剂型，从而导致更安全的儿科配方和改善的患者依从性。 公共卫生相关性：由于依从性差，临时配方和危险的药物错误，小儿药物配方不足会损害儿童疾病的有效治疗。问题的基础是可口的，准确的给药和适合年龄的剂量格式的挑战。需要开发现有成人药品的儿科重新印度的用户友好，廉价的开发平台，以使用受控的释放速度管理味觉掩盖的活性药物成分（API）。该项目使用模型苦涩API，旨在测试精密粒子织物技术的可行性，以产生可口，适合年龄和准确的剂量，以此作为更安全的儿科药物和更好合规性的一种手段。