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: 8780181
• 负责人: Nathan H Dormer
• 金额: $ 77.55万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780181
• 关键词: Acids; Address; Adolescent; Adult; Age; Agreement; Appearance; Architecture; Area; Biological Availability; Caliber; Capital Financing; Child; Childhood; Crossover Design; Development; Disease; Dosage Forms; Dose; Drug Formulations; Drug Kinetics; Engineering; Ensure; Evaluation; Exhibits; Female; Flavoring; Foundations; Gastrointestinal tract structure; Genetic Crossing Over; Goals; Health; Hospitals; Human; In Vitro; Ingestion; Liquid substance; Masks; Medication Errors; Medicine; Microcapsules drug delivery system; Modeling; Oral; Oral cavity; Particle Size; Pediatric Hospitals; Performance; Pharmaceutical Preparations; Pharmacists; Pharmacologic Substance; Phase; Placebos; Population; Powder dose form; Prednisone; Process; Property; Provider; Randomized; Relative (related person); Risk; Ritonavir; Sampling; Shapes; Simulate; Small Business Innovation Research Grant; Smell Perception; Solid; Solutions; Stomach; Surface; Suspension substance; Suspensions; Tablets; Taste Perception; Techniques; Technology; Therapeutic Equivalency; Time; Water; Weight; Work; base; capsule; compliance behavior; controlled release; cost effective; design; dosage; effective therapy; flexibility; hedonic; improved; in vivo; innovation; liquid formulation; male; meetings; neonate; particle; prednisolone; programs; screening; seal; success; user-friendly

DESCRIPTION (provided by applicant): New dosage forms are needed to address the shortcomings of current practice with regard to administration of medications to pediatric populations. Specifically, in the absence of pediatric-specific products - formulations that are both palatable (to ensure compliance) and titratable (to meet the weight/surface area- appropriate dosage) - providers either utilize adult-approved liquid formulations or manipulate available products to create extemporaneous formulations (e.g., by crushing a tablet). Liquid suspensions, while titratable and largely preferred by children over tablets and capsules, are often poorly palatable and thus suffer from poor compliance. Ad-hoc formulations can also alter the performance and risk the likelihood of under or over-dosing. Orbis Biosciences's has developed a free-flowing drug-loaded microcapsule-based powder that will taste-mask bitter pharmaceutical actives during ingestion and exhibit complete dosage form dissolution in the gastrointestinal tract. This microcapsule platform is made possible by utilizing Precision Particle Fabrication (PPF) to place a pH-responsive shell over a solid-dispersed core of poorly water-soluble drug in a water-free, single step process. The first product to use Orbis's microcapsule approach to taste masking will be ORB-101, a prednisone-loaded microcapsule formulation. Upon successful FDA approval, ORB-101 will compete with oral liquid formulations or prednisone and prednisolone, products that suffer from poor palatability. Under the Phase I SBIR work, Orbis successfully developed two formulations, ORB-101 and ORB-102, containing prednisone and ritonavir, respectively. The microcapsule powders were able to: (1) reduce the presence of prednisone and ritonavir in neutral dissolution medium at 2 minutes by 55 and 92% respectively, compared to the RLD syrups for these two drugs, and (2) still exhibit 100% dissolution by 30 minutes when placed in acidic medium. The objective of this Phase II proposal is to optimize the prednisone formulation (ORB-101) into a shelf-stable powder in vitro (Aim 1), verify it's superior palatability compared to the RLD in a human taste screening (Aim 2), and demonstrate its bioequivalence to the RLD in a human pharmacokinetic study (Aim 3). The completion of this Phase II SBIR program will facilitate the efficient and timely submission of an IND filing to the FDA (Phase III SBIR) and have an immediate and lasting impact on the best practices for treating prednisone-responsive pediatric disorders by: (1) establishing the improved palatability or ORB-101 in the first human trials while, (2) readying ORB-101 and the PPF platform on which it is based for a co- development agreement or venture capital funding.

描述（由申请人提供）：需要新的剂型来解决目前对儿科人群用药的实践中的缺陷。具体来说，在缺乏儿科专用产品的情况下——既可口（以确保合规性）又可滴定（以满足体重/表面积——适当剂量）的配方——提供者要么利用成人批准的液体配方，要么操纵现有产品来创造临时配方（例如，通过压碎片剂）。液体悬浮液虽然可滴定，并且比片剂和胶囊更受儿童欢迎，但往往适口性较差，因此依从性差。特殊配方还可能改变性能并带来剂量不足或过量的风险。 Orbis Biosciences 开发了一种自由流动的载药微胶囊粉末，可在摄入过程中掩盖苦味药物活性物质的味道，并在胃肠道中表现出完全的剂型溶解。该微胶囊平台是通过利用精密颗粒实现的 制造 (PPF)，以无水、单步过程将 pH 响应外壳放置在难溶性药物的固体分散核心上。第一个使用 Orbis 微胶囊方法掩味的产品是 ORB-101，这是一种负载泼尼松的微胶囊配方。一旦获得 FDA 批准，ORB-101 将与口服液体制剂或适口性较差的泼尼松和泼尼松龙产品竞争。在第一期 SBIR 工作中，Orbis 成功开发了两种制剂 ORB-101 和 ORB-102，分别含有泼尼松和利托那韦。微胶囊粉末能够：(1) 与这两种药物的 RLD 糖浆相比，2 分钟内中性溶出介质中泼尼松和利托那韦的含量分别减少 55% 和 92%，并且 (2) 仍然表现出 100% 溶出度当置于酸性介质中时，30分钟。该 II 期提案的目标是将泼尼松配方 (ORB-101) 优化为体外储存稳定的粉末（目标 1），在人类味觉筛选中验证其与 RLD 相比的优越适口性（目标 2），以及在人体药代动力学研究中证明其与 RLD 的生物等效性（目标 3）。该 II 期 SBIR 计划的完成将有助于高效、及时地向 FDA 提交 IND 申请（III 期 SBIR），并通过以下方式对治疗泼尼松反应性儿科疾病的最佳实践产生直接和持久的影响：(1)在首次人体试验中确定 ORB-101 的适口性得到改善，同时 (2) 为 ORB-101 及其所基于的 PPF 平台做好共同开发协议或风险投资融资的准备。