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: 8935865
• 负责人: Nathan H Dormer
• 金额: $ 56.06万
• 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 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8935865
• 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; 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在给儿科人群用药方面的不足。具体地说，在没有儿科专用产品的情况下--配方既适口(以确保遵从性)，又可滴定(以满足重量/表面积-适当的剂量)--提供者要么使用成人批准的液体配方，要么操纵现有产品来创建即兴配方(例如，通过粉碎片剂)。液体悬浮剂虽然可以滴定，而且在很大程度上受到儿童的青睐，而不是片剂和胶囊，但往往口感不佳，因此依从性较差。特殊配方还可以改变性能，并有可能出现剂量不足或过量的风险。奥比斯生物科学公司已经开发出一种自由流动的载药微胶囊粉末，这种粉末将在摄入过程中掩盖苦味药物活性，并在胃肠道中表现出完全的剂型溶解。这种微胶囊平台是通过使用Precision颗粒物来实现的 制备(PPF)在无水的单步工艺中，在难于溶于水的药物的固体分散核心上放置对pH响应的外壳。第一个使用奥比斯的微胶囊方法来掩盖味道的产品将是ORB-101，一种加载泼尼松的微胶囊配方。一旦FDA成功批准，ORB-101将与口服液制剂或强的松和强的松龙竞争，这些产品的适口性较差。在第一阶段的SBIR工作中，Orbis成功地开发了两种制剂，ORB-101和ORB-102，分别含有泼尼松和利托那韦。与RLD糖浆相比，微囊粉剂可使中性溶出介质中强的松和利托那韦的溶出度分别降低55%和92%，在酸性介质中放置30min仍有100%的溶出度。此第二阶段方案的目标是将泼尼松制剂(ORB-101)优化为体外货架稳定的粉末(目标1)，在人类味觉筛选(目标2)中验证其相对于RLD的优越适口性，并在人体药代动力学研究(目标3)中证明其与RLD的生物等效性。这一第二阶段SBIR计划的完成将有助于高效和及时地向FDA提交IND申请(第三阶段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即时和持久的影响：(1)在第一次人体试验中建立改善的适口性或ORB-101，同时(2)为共同开发协议或风险资本资助准备ORB-101及其所基于的PPF平台。