Age-appropriate flexible pediatric drug delivery systems

适合年龄的灵活儿科给药系统

• 批准号: 10509397
• 负责人: MANSOOR A KHAN
• 金额: $ 34.18万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10509397
• 关键词: 3D Print; Address; Adult; Adverse event; Age; Animals; Anti-Retroviral Agents; Biological Availability; Businesses; Child; Childhood; Clinical; Color; Computer software; Data; Deglutition; Development; Diamond; Diclofenac; Dosage Forms; Dose; Drops; Drug Combinations; Drug Compounding; Drug Delivery Systems; Drug Formulations; Drug Modelings; Drug usage; Ensure; Environment; Equipment; Formulation; Fumarates; HIV resistance; Health Professional; Hospitals; Hour; Incidence; Lamivudine; Lasers; Life; Liquid substance; Lopinavir; Methods; Modeling; National Institute of Child Health and Human Development; Oral; Overdose reduction; Pediatrics; Pharmaceutical Preparations; Pharmacists; Pharmacopoeias; Pharmacy facility; Phenytoin; Physicians; Physiology; Population; Powder dose form; Preparation; Printing; Probability; Process; Recycling; Reporting; Resources; Safety; Scanning; Scientist; Shapes; Solid; Sterility; System; Tablets; Taste preferences; Tenofovir; Testing; Therapeutic; Thinness; Time; Tongue; Translating; United States; United States Food and Drug Administration; age group; appropriate dose; base; capsule; comparative; cost effective; dosage; efficacy evaluation; epivir; flexibility; innovation; melting; microbial; novel strategies; pediatric patients; pediatrician; pharmacokinetics and pharmacodynamics; safety assessment; tablet formulation; 3D Print; Address; Adult; Adverse event; Age; Animals; Anti-Retroviral Agents; Biological Availability; Businesses; Child; Childhood; Clinical; Color; Computer software; Data; Deglutition; Development; Diamond; Diclofenac; Dosage Forms; Dose; Drops; Drug Combinations; Drug Compounding; Drug Delivery Systems; Drug Formulations; Drug Modelings; Drug usage; Ensure; Environment; Equipment; Formulation; Fumarates; HIV resistance; Health Professional; Hospitals; Hour; Incidence; Lamivudine; Lasers; Life; Liquid substance; Lopinavir; Methods; Modeling; National Institute of Child Health and Human Development; Oral; Overdose reduction; Pediatrics; Pharmaceutical Preparations; Pharmacists; Pharmacopoeias; Pharmacy facility; Phenytoin; Physicians; Physiology; Population; Powder dose form; Preparation; Printing; Probability; Process; Recycling; Reporting; Resources; Safety; Scanning; Scientist; Shapes; Solid; Sterility; System; Tablets; Taste preferences; Tenofovir; Testing; Therapeutic; Thinness; Time; Tongue; Translating; United States; United States Food and Drug Administration; age group; appropriate dose; base; capsule; comparative; cost effective; dosage; efficacy evaluation; epivir; flexibility; innovation; melting; microbial; novel strategies; pediatric patients; pediatrician; pharmacokinetics and pharmacodynamics; safety assessment; tablet formulation

ABSTRACT/SUMMARY Pediatric medications require dose flexibility to obtain desired therapeutic concentration. Most medications are produced for adults as capsules and tablets, which are often not suitable for children. The lack of or limited availability of medications for the pediatrics population is primarily due to the evolving physiology of children where fixed dosage forms do not work. Extemporaneous formulations are a common way to adjust the dose of the drug for pediatrics patient. However, concerns have been raised regarding lack of dose accuracy, stability, bioavailability and consistency for such formulations by healthcare professionals and FDA. Quality, safety and efficacy concerns of extemporaneous preparations can be addressed by printing medications by selective laser sintering (SLS) 3D printing method as supported by preliminary data. The SLS method is ideally suited to print precision dosage forms in a clinical hospital environment, and has dose-flexibility, multiple drug incorporation capability, short-time to print, minimal material requirement, low-power needs, and small footprint of the equipment. Doses can easily be adjusted by number of printed layer since printing is performed by layering mechnaism. The objective of the proposal is to demonstrate the feasibility of printing dose-flexible pediatric delivery system (printlets) using selective laser sintering (SLS). Tenofovir disoproxil fumarate and lamivudine will be used as model drugs, as both drugs are commonly used alone or in combination in pediatric patients. However, only a single strength combination product (of both drugs) is commercially available. Administering these drugs as age appropriate flexible pediatric delivery systems will reduce overdose and underdose, which is the case with extemporaneous preparation intended for pediatric population. This would be translated into lower incidence of adverse events and reduce probability of development of HIV resistance to medications when underdose. Furthermore, dose-flexible pediatric delivery systems should meet quality criteria of FDA, and should be stable during shelf-life and usage periods besides being effective. The delivery systems will be tested as per FDA and USP recommended tests to ensure quality. Pediatric delivery systems will be tested for long-term, accelerated and in-use stability conditions. Safety and efficacy will be demonstrated by comparative pharmacokinetics and pharmacodynamics studies between dose flexible pediatric delivery system and commercial tablets formulation. The PI of the proposal led the FDA team of scientists and reviewers to the approval of the first and only 3D printed drug product (Spritam®). Following are the specific aims of the proposal: Aim I: To demonstrate the feasibility of printing pediatric delivery systems (printlets) of combination drugs (tenofovir disoproxil fumarate and lamivudine) by selective laser sintering in short timeframes (<2 hours), characterize the quality and assess stability that will meet United States Pharmacopeia (USP) and Food and Drug Administration (FDA) requirements of identity, quality, purity, and strength. Aim II: To demonstrate the safety and efficacy of flexible pediatric delivery systems (printlets) by pharmacokinetics and pharmacodynamics studies.

摘要/摘要 小儿药物需要剂量灵活性才能获得所需的治疗浓度。大多数药物是生产的 对于成年人作为胶囊和片剂，通常不适合儿童。缺乏药物可用性或有限 对于儿科人群，主要是由于固定剂型不起作用的儿童不断发展的生理学。 临时公式是调整儿科患者药物剂量的常见方法。但是，担心 由于缺乏剂量准确性，稳定性，生物利用度和此类公式的一致性而提出了 医疗保健专业人员和FDA。可以解决扩展精美准备的质量，安全性和效率问题 通过初步数据支持的选择性激光烧结（SLS）3D打印方法打印药物。 SLS 理想的方法适合在临床医院环境中打印精度剂型，并且具有多种剂量，多剂量 药品行业能力，短时印刷，最少的材料需求，低功率需求和少量足迹 设备。剂量可以通过印刷层的数量轻松调整，因为通过分层机械性执行印刷层。 该提案的目的是证明印刷剂量富足的儿科递送系统（Printlets）的可行性 使用选择性激光烧结（SLS）。替诺福韦毒素富马酸酯和拉米夫丁将被用作模型药物，因为 药物通常单独使用或在小儿患者组合使用。但是，只有一个强度组合产品 （两种药物的）可商购。作为适合年龄的柔性小儿输送系统，管理这些药物 将减少用药过量和用药不足，这种情况是针对小儿人群的广泛准备。 这将转化为不良事件的较低事件，并降低抗HIV抗性的可能性 服用不足时服用药物。此外，剂量富足的儿科输送系统应符合FDA的质量标准， 并且在保质期和使用期内应该保持稳定。交付系统将根据 FDA和USP建议测试以确保质量。小儿输送系统将长期测试，加速和 使用中的稳定性条件。比较药代动力学将证明安全性和效率 剂量柔性儿科递送系统和商业片剂配方之间的药学动力学研究。 pi的pi 该提案导致FDA科学家和审阅者团队获得了第一和唯一的3D印刷药品的批准 （Spritam®）。以下是该提案的具体目的： 目的I：展示印刷小儿递送系统（Printlets）组合药物的可行性（Tenofovir 通过在短时间（<2小时）中进行选择性激光烧结，富马酸和拉米夫氏蛋白酶的毒素毒素和拉米夫丁）表征了质量 并评估将符合美国药房（USP）和食品和药物管理局（FDA）的稳定性 身份，质量，纯度和力量的要求。 AIM II：通过药代动力学和 药效学研究。