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）：需要新的剂型表格来解决有关在儿科种群中服用药物的当前实践的缺点。具体而言，在不存在小儿特异性产品的情况下 - 既可口的配方（以确保合规性）和可滴定性（满足体重/表面积 - 适当的剂量） - 提供商要么使用成人批准的液体配方，要么使用可用的产品来创建末代配方（例如，通过粉碎片剂）。液体悬浮液虽然可滴定且在很大程度上受到儿童优于片剂和胶囊的偏爱，但通常不太可口，因此依从性不佳。临时配方还可以改变性能，并冒着过度剂量或过度剂量的可能性。 Orbis Biosciences已经开发了一种自由流动的药物基于微胶囊的粉末，该粉末将在摄入过程中掩盖掩盖苦味药物活性剂，并在胃肠道中表现出完全剂量的溶解。通过利用精确粒子使这个微胶囊平台成为可能 制造（PPF）将pH响应性的壳放在无水溶解药物的固体分散核心上，在无水的单步过程中。使用Orbis微胶囊味掩模的第一种产品是Orb-101，是泼尼松的微胶囊配方。在成功获得FDA批准后，ORB-101将与口服液体配方，泼尼松和泼尼松龙竞争，这些产品的适口性差。 在I期SBIR工作下，Orbis成功地开发了两种配方ORB-101和ORB-102，分别包含泼尼松和利托纳维尔。微胶囊粉末能够：（1）与这两种药物的RLD糖浆相比，在2分钟下，在2分钟下降低了中性分解培养基中的泼尼松和利托那韦的存在，（2）在酸性培养基中时仍将100％溶解。该II期提案的目的是将泼尼松的配方（ORB-101）优化为货架稳定的粉末体外（AIM 1），验证与人类味觉筛查中的RLD相比，它具有优越的可口性（AIM 2），并在人类药物学研究中证明了其与RLD的生物等效性（AIM 3）。 该II阶段SBIR计划的完成将有助于及时提交给FDA（III阶段SBIR），并直接且持久地影响对治疗泼尼松响应性儿科疾病的最佳实践，以：它是基于共同开发协议或风险投资资金的。