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

项目摘要/摘要：连续制造监管科学的发展 能够实时释放的基于薄膜的药物剂型 近年来，聚合物薄膜已成为一种很有前途的药物输送平台。 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(舌下)或面颊内侧(口腔)，用于药物的持续释放。这些电影提供了 与传统的口腔崩解片(ODT)相比，有几个明显的优势，部分原因是它们的体积小，容易 管理的灵活性和脆弱性比药物替代疗法更高。因此，他们获得了极大的兴趣，因为 一种新兴的新型口服给药系统。然而，与可以支持的大量可用知识不同 关于平板电脑的稳健和可预测的制造，与条带薄膜相关的文献相当稀少和零散。 我们团队在过去的八年里一直致力于这项新技术的研究，并已经证明，如果制定得当 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，制造。我们已经证明，与流行的基于溶剂的 通过浆料浇注，可以将纳米和微米尺寸的工程药物颗粒结合在一起，以实现 高质量的薄膜，具有极佳的药物含量均匀度，即使从较差的水中也能非常快地释放 可溶药物。其他吸引人的特点包括配制药物的能力，包括那些高度水分的药物 不溶，用于许多重要的治疗应用，如速效疼痛管理、速效药物 对于恶心和呕吐，治疗阿尔茨海默病的药物通常会导致吞咽困难(吞咽困难 治疗癌症或艾滋病所需的联合疗法，以及最重要的是，解决未得到满足的 治疗在儿科制剂中的需要，例如，新生儿的药物输送需要灵活的剂量，取决于 婴儿的体重，以及儿童癌症。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 作为连续带状薄膜关键产品质量属性的关键制造工艺和参数 制造业。此外，我们将开发和验证关键流程的模型，以实现改进的产品和 流程开发。因此，拟议的工作将导致发展重要的知识体系， 是支持更稳健、可预测或更具成本效益的工艺以改进薄膜制造所必需的 以高质量为基础的剂型。它还将支持更有效地监管电影产品。 FDA，从而造福于患者和社会。

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.