Development of regulatory science for continuous manufacturing of strip-film based drug dosage forms capable of real-time release

连续生产可实时释放的带状薄膜药物剂型监管科学的发展

• 批准号: 9143981
• 负责人: Rajesh Dave
• 金额: $ 30万
• 依托单位: NEW JERSEY INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9143981
• 关键词: Development; regulatory; science; continuous; manufacturing

Project Summary/Abstract: Development of regulatory science for continuous manufacturing of strip-film based drug dosage forms capable of real-time release Polymer films have emerged as a promising platform for the delivery of pharmaceutical products in recent years. They are roughly the size of a postage stamp and can be placed on the tongue for immediate release or under the tongue (sublingual) or on the inside of the cheek (buccal) for sustained release to deliver drugs. These films offer several distinct advantages over traditional orally disintegrating tablets (ODTs), in part due to their small size, ease of administration and more flexibility and less fragility than ODTs. Therefore they are gaining significant interest as an emerging novel oral drug delivery system. However, unlike the vast body of available knowledge to support robust and predictable manufacturing of tablets, the literature related to strip-films is rather sparse and fragmented. Our group has been working on this novel technology for past eight years and has shown that if properly formulated and manufactured in a continuous process, this is a technology that has the potential to modernize pharmaceutical manufacturing due to its many attractive features. We have shown that in contrast to prevalent solvent based casting, engineered drug particles in nano and micro sizes may be incorporated through slurry casting for achieving high quality films that have excellent drug content uniformity and lead to very fast release even from poorly water soluble drugs. Other attractive features include the ability to formulate drugs, including those that are highly water insoluble, for many important therapeutic applications, such as quick-effect pain management, fast-acting remedy for nausea and vomiting, medications for Alzheimer’s disease which often leads to dysphagia (inability to swallow tablets), combination therapies required for treating cancer or AIDS, and most importantly, addressing unmet therapeutics needs in pediatric formulations, e.g., drug delivery in neonates requiring flexible dosages depending on the weight of the infant, and in pediatric cancers. To realize the full potential of this emerging technology, we propose to carry out scientific research to determine the impact of raw and intermediate material properties as well as key manufacturing processes and parameters on critical product quality attributes in continuous strip-film manufacturing. Further, we will develop and validate models for key processes to enable improved product and process development. Thus the proposed work will lead to the development of the important body of knowledge that is necessary to support more robust, predictable, or cost-effective processes for improved manufacturing of film based dosage forms that achieve high quality. It will also support more efficient regulation of the film products by the FDA, thus benefitting patients as well as society.

项目概要/摘要：连续制造监管科学的发展 能够实时释放的基于条状薄膜的药物剂型 近年来，聚合物膜已经成为用于递送药物产品的有前景的平台。 它们大约有邮票大小，可以放在舌头上立即释放，也可以放在舌头下面。 舌（舌下）或脸颊内侧（颊）上，用于持续释放以递送药物。这些电影提供 与传统的口腔崩解片（ODT）相比，它具有几个明显的优势，部分原因是它们尺寸小、易于崩解 与ODT相比，它具有更大的管理灵活性和更小的脆弱性。因此，他们获得了极大的兴趣， 一种新兴的新型口服给药系统。然而，与大量可用的知识支持不同， 尽管片剂的生产是可靠和可预测的，但与条带膜相关的文献相当稀少和零散。 我们的团队在过去的八年里一直致力于这项新技术，并已表明，如果制定得当， 并在一个连续的过程中生产，这是一项有潜力使制药现代化的技术， 由于它的许多吸引人的特点。我们已经表明，与普遍的溶剂型相比， 通过流延，纳米和微米尺寸的工程药物颗粒可以通过浆料流延并入，以实现 具有优异的药物含量均匀性并导致非常快速释放的高质量膜， 可溶性药物其他有吸引力的功能包括制定药物的能力，包括那些高度水 不溶性，用于许多重要治疗应用，例如速效疼痛管理、速效药物 用于恶心和呕吐，治疗阿尔茨海默病的药物，通常会导致吞咽困难（无法吞咽 片剂），治疗癌症或艾滋病所需的联合疗法，最重要的是，解决未满足的 儿科制剂的治疗需求，例如，需要灵活剂量的新生儿给药， 婴儿的体重和儿童癌症。为了充分发挥这项新兴技术的潜力，我们 建议开展科学研究，以确定原材料和中间材料性能的影响，以及 作为关键生产工艺和参数对连续条膜中关键产品质量属性的影响 制造业此外，我们还将开发和验证关键流程的模型，以改进产品， 工艺开发因此，拟议的工作将导致发展重要的知识体系， 对于支持更稳健、可预测或成本有效的工艺以改进膜的制造是必要的 以实现高质量的剂型为基础。它还将支持更有效地监管电影产品， FDA，从而使患者和社会受益。