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）：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特异性测试到可口的风味特征和有效的递送形式。一本小说 掩盖药物苦味，同时提供剂量设计和形式灵活性的技术将使现有成人药品配方成为专门为儿科患者设计的药物。我们提出的策略使用精密颗粒制造（PPF）来开发儿科载药微粒，可以掩盖苦味并允许灵活的剂量和形式。 PPF技术的核心优势在于其对颗粒尺寸、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平台，用于微胶囊化难吃的儿科活性药物成分 (API)。我们假设，PPF 生产的均匀、精确设计的微粒将为儿科药物创造有效的味道掩蔽配方，同时还允许活性剂在消化条件下快速、受控释放。我们进一步假设，这种强大的微粒策略将允许准确、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并表征含有精确控制的物理化学特征的含苦味 API 的微粒模型，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味性能（目标 2）。结果将是载药微粒模型，该微粒符合基于粒径、均匀性和药物表面浓度的适口性标准，并且可以根据消化条件下所需的释放曲线进行定制。在确定精确设计这些微粒的可行性后，第二阶段将重点关注味道和口感等感官特性的临床评估，以及剂量准确性、滴定和形式灵活性的演示。这种基于 PPF 的封装策略解决了儿科药物的适口性、剂量准确性和形式灵活性问题，同时改进了现有的封装技术，这些技术成本高昂、耗时，并且会产生控制不佳、异质批次的微粒。此外，该PF技术对多种药物和基质/包衣材料以及大规模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，用于创建可口的、适合年龄的和准确的剂型，从而获得更安全的儿科配方并提高患者的依从性。 公共卫生相关性：由于依从性差、配方特殊和危险的用药错误，儿科药物配方不足会损害儿童疾病的有效治疗。问题的根源在于适口性、准确剂量和适合年龄的剂型挑战。需要开发一个用户友好、廉价的开发平台，用于对现有成人药品进行儿科重新配制，以控制释放速率施用掩味活性药物成分 (API)。该项目旨在使用苦味 API 模型来测试精密颗粒制造技术生产适口、适合年龄和准确剂量的可行性，作为更安全的儿科药物和更好的依从性的手段。