Novel 3D Printed Architectures for Oral Long-acting Drug Delivery Systems

用于口服长效给药系统的新型 3D 打印架构

• 批准号: 9347072
• 负责人: Andrew Martin Bellinger
• 金额: $ 22.5万
• 依托单位: LYNDRA THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347072
• 关键词: 3D Print; Ache; Adherence; Adoption; Antipsychotic Agents; Architecture; Biomedical Engineering; Businesses; Caregivers; Chemical Engineering; Chronic; Chronic Disease; Clinical; Complex; Deposition; Development; Dosage Forms; Dose; Drug Delivery Systems; Drug Stability; Elements; Enteral; Formulation; Frequencies; Geometry; Goals; Grant; Hospitalization; Hour; In Vitro; Injectable; Injection of therapeutic agent; Intramuscular Injections; Island; Kinetics; Length; Mechanics; Medical; Mental disorders; Methodology; Methods; Modeling; Modification; Molds; Oral; Outcome; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; Phase; Physicians; Polymers; Printing; Property; Regimen; Relapse; Risperidone; Schizophrenia; Sea; Small Business Innovation Research Grant; Solid; Stomach; Structure; System; Techniques; Technology; Therapeutic; Time; Toxicology; Variant; Welding; arm; base; capsule; caregiver interventions; compliance behavior; cost effective; design; dosage; efficacy study; experience; flexibility; improved; in vivo; manufacturing process; mechanical properties; medication compliance; melting; multidisciplinary; novel; patient population; phase 1 study; pill; pre-clinical; premature; productivity loss; residence; safety study; small molecule; stability testing; symptom management

Novel 3D Printed Architectures for Oral Long-Acting Drug Delivery Systems Project Summary Long-acting oral (LAO) dosage forms may offer significant benefits for managing chronic medical conditions requiring long-term and intensive medication regimens, particularly those in which observed therapy would be practical and advantageous, such as psychiatric disorders. Poor patient adherence and persistence to therapy are a significant challenge in the schizophrenia patient population, leading to relapse, hospitalizations, and loss of productivity. Extended drug delivery reduces dosing frequency, alleviates pill burden on patients and caregivers, and improves medication adherence. Compared to intramuscular injections, oral dosage forms may improve adoption among patients and clinicians and are cost-effective and more easily administered. Lyndra has developed a LAO delivery system based on a gastric residence technology that can achieve sustained therapeutic drug levels in-vivo for over one week. Lyndra’s LAO therapies have complex geometry, multiple polymeric material components, and intricate assembly and manufacturing requirements involving extrusion, injection molding, and welding. 3D printing is an alternative manufacturing methodology with substantial practical advantages. Novel internal microarchitectures that can only be achieved with 3D printing (3DP) have the potential to overcome challenges with zero-order release kinetics and enable tunable mechanical properties to favor safe gastric residence and exit. The goal of this grant is to develop a novel manufacturing method using fused deposition modeling based 3DP techniques to create novel microarchitectures that enhance the drug delivery and mechanical properties of LAO formulations of risperidone. 3DP provides precise control over the geometry and composition of Lyndra’s solid oral polymeric systems and enables easy modification of dosage form parameters to suit different drug profiles. We believe that this approach will produce high-quality LAO formulations with customizable release profiles and mechanical strength to substantially improve real world performance. In Aim 1 we will focus on optimizing architectures to achieve near linear in-vitro release rates. In Aim 2 and 3, we will focus on fabricating architectures with structural elements for improving the mechanical stability of the drug-loaded segments and the linkages connecting adjacent drug-loaded segments in the formulation. Successful proof-of-concept 3DP Phase I studies will lead to a Phase II SBIR that would include preclinical in-vivo pharmacology and safety studies, stability testing, GMP methods of 3DP manufacturing, and IND-enabling toxicology. Novel LAO therapies may offer improved treatment paradigms for patients with schizophrenia and other chronic diseases.

用于口服长效给药系统的新型3D打印结构 项目摘要 长效口服(LAO)剂型可能为管理慢性药物提供显著益处 需要长期和密集用药方案的情况，特别是在观察到 治疗将是实用和有利的，例如精神障碍。患者依从性差， 在精神分裂症患者群体中，坚持治疗是一个重大挑战，导致 复发、住院和生产力下降。延长给药时间减少了给药频率， 减轻患者和护理人员的服药负担，提高服药依从性。与.相比 肌肉注射、口服剂型可能会促进患者和临床医生的采用，并 性价比高，更易于管理。Lyndra开发了一种老挝交付系统，该系统基于 胃滞留技术，可在体内实现持续治疗药物浓度超过一周。 Lyndra的LAO疗法具有复杂的几何结构，多种聚合物材料成分，以及 复杂的装配和制造要求，包括挤出、注塑和焊接。 3D打印是一种具有实质性实用优势的替代制造方法。小说 只能通过3D打印(3DP)实现的内部微体系结构有可能 用零级释放动力学克服挑战，使可调的机械性能有利于 安全的胃居留和离开。 这笔赠款的目标是开发一种使用熔融沉积建模的新制造方法 基于3DP技术创建新的微体系结构，以增强药物输送和机械 利培酮劳氏制剂的性质。3DP提供对几何体的精确控制 Lyndra的固体口服聚合物系统的组合物，使剂型易于修改 参数，以适应不同的药物配置。我们相信，这一方法将产生高质量的老挝 具有可定制的释放配置文件和机械强度的配方，可显著提高REAL 世界表演。在目标1中，我们将专注于优化结构以实现接近线性的体外培养 放映率。在目标2和目标3中，我们将专注于构建具有以下结构元素的体系结构 提高载药节段和连接相邻节段的机械稳定性 配方中的载药片段。成功的概念验证3DP第一阶段研究将导致 第二阶段SBIR，包括临床前体内药理学和安全性研究、稳定性测试、GMP 3DP的制造方法和IND-Enabling毒理学。新的老挝疗法可能会提供改进的 精神分裂症和其他慢性病患者的治疗范例。