Development Of Regulatory Science For Continuous Manufacturing Of Strip-Film Based Drug Dosage Forms Capable Of Real-Time Release

Project Summary/Abstract: Development of regulatory science for continuous manufacturingof strip-film based drug dosage forms capable of real-time releasePolymer 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 thetongue (sublingual) or on the inside of the cheek (buccal) for sustained release to deliver drugs. These films offerseveral distinct advantages over traditional orally disintegrating tablets (ODTs), in part due to their small size, easeof administration and more flexibility and less fragility than ODTs. Therefore they are gaining significant interest asan emerging novel oral drug delivery system. However, unlike the vast body of available knowledge to supportrobust 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 formulatedand manufactured in a continuous process, this is a technology that has the potential to modernize pharmaceuticalmanufacturing due to its many attractive features. We have shown that in contrast to prevalent solvent basedcasting, engineered drug particles in nano and micro sizes may be incorporated through slurry casting for achievinghigh quality films that have excellent drug content uniformity and lead to very fast release even from poorly watersoluble drugs. Other attractive features include the ability to formulate drugs, including those that are highly waterinsoluble, for many important therapeutic applications, such as quick-effect pain management, fast-acting remedyfor nausea and vomiting, medications for Alzheimer�s disease which often leads to dysphagia (inability to swallowtablets), combination therapies required for treating cancer or AIDS, and most importantly, addressing unmettherapeutics needs in pediatric formulations, e.g., drug delivery in neonates requiring flexible dosages depending onthe weight of the infant, and in pediatric cancers. To realize the full potential of this emerging technology, wepropose to carry out scientific research to determine the impact of raw and intermediate material properties as wellas key manufacturing processes and parameters on critical product quality attributes in continuous strip-filmmanufacturing. Further, we will develop and validate models for key processes to enable improved product andprocess development. Thus the proposed work will lead to the development of the important body of knowledge thatis necessary to support more robust, predictable, or cost-effective processes for improved manufacturing of filmbased dosage forms that achieve high quality. It will also support more efficient regulation of the film products by theFood and Drug Administration, thus benefitting patients as well as society.