Review: Continuous Manufacturing of Small Molecule Solid Oral Dosage Forms

Abstract

Continuous manufacturing (CM) is defined as a process in which the input material(s) are continuously fed into and transformed, and the processed output materials are continuously removed from the system. CM can be considered as matching the FDA’s so-called ‘Desired State’ of pharmaceutical manufacturing in the twenty-first century as discussed in their 2004 publication on ‘Innovation and Continuous Improvement in Pharmaceutical Manufacturing’. Yet, focused attention on CM did not really start until 2014, and the first product manufactured by CM was only approved in 2015. This review describes some of the benefits and challenges of introducing a CM process with a particular focus on small molecule solid oral dosage forms. The review is a useful introduction for individuals wishing to learn more about CM.

A Continuous Process for Manufacturing Apremilast. Part II: Process Characterization to Establish a Parametric Control Strategy

“…Integrated continuous manufacturing (CM) has emerged as a compelling potential alternative to traditional batch processing for synthetic drug substance manufacturing in some scenarios. − However, this remains a relatively new mode of manufacturing for the industry, and as such, drug substance process development teams are still refining the approach to process characterization (PC) and the control strategy to accompany such processes…”

Towards the Continuous Manufacturing of Liquisolid Tablets Containing Simethicone and Loperamide Hydrochloride with the Use of a Twin-Screw Granulator

“…It eliminates the need to stop and move intermediates between production steps, which can potentially improve the quality of the final pharmaceutical product. Therefore, leaders in the pharmaceutical industry are interested in this technology, which compared to the traditional manufacturing process, speeds up the production cycle, improves overall efficiency, and significantly reduces costs [3,4].…”

Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

“…Thus, CM can enable rapid development of robust tablets and capsules in a cost-efficient manner . As a result, over the past decade, CM has gained widespread attention, leading to the approval of several new commercial drug products, including Orkambi (lumacaftor/ivacaftor), Verzenio (abemaciclib), , Daurismo (glasdegib maleate), Duvroq (daprodustat), , and Cibinqo (abrocitinib) . Advancements in technology have also led to the development of several platform technologies based on CM …”