Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters

Abstract

A c c e p t e d M a n u s c r i p t Highlights  HME can be exploited in a broad range of applications for advanced drug delivery  Unique advantages to be utilised in a solvent free manufacturing platform  A means to explore the potential of continuous manufacture of pharmaceuticals  Scale-up issue considerations, from an FDA compliance point of view  HME regulatory guidelines for the manufacture of novel drug delivery systems Ali NokhodchiAli Nokhodchi is a professor of pharmaceutics and drug delivery at the University of Sussex. He has supervised over 120 Mpharm, PharmD, and MSc students and 15 PhD postgraduate students at several institutions in various fields of pharmaceutical formulations and drug delivery. He is an editorial board member of over 20 peer-reviewed international journals. Ali has published over 185 research articles in various fields of pharmaceutics, including tableting, particle engineering, inhalation, nanoparticles, dissolution, skin delivery, and controlled-release formulations. In addition, he has published five book chapters on skin, controlled-release formulations, particle engineering, and inhalation products. Ali has also been the editor of a book on pulmonary delivery published by Wiley in 2015. He has been the recipient of several prizes in pharmaceutical sciences and has been listed by Essential Science Indicators in the top 1% scientists in the field of pharmacology and toxicology.Currently, because globalization, the pharmaceutical industry is facing enormous challenges to comply with regulatory matters. Reduced patent life and overall decreased profitability of newly discovered drugs are also forcing the pharmaceutical industry to shorten the drug development time with maximum throughput. Therefore, continuous manufacturing (CM) processes via hot melt extrusion (HME) can be a promising alternative for achieving these goals. HME offers solvent-free green technology with a process that is easy to scale up. Moreover, CM provides better product quality assurance compared with batch processes, with fewer labor costs and shorter time to development. In this review, we primarily focus on various aspects of CM and the emerging application of HME to bridge the current manufacturing gap in pharmaceutical sphere.

In-Line UV-Vis Spectroscopy as a Fast-Working Process Analytical Technology (PAT) during Early Phase Product Development Using Hot Melt Extrusion (HME)

“…Pharmaceutical HME process can improve the bioavailability of poorly water-soluble drugs by the formation of solid solutions or solid dispersions [5,6,7]. Recently, AstraZeneca commercialized HME-based tablets Lynparza ® (olaparib) for breast and ovarian cancer [8].…”

Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus

“…Diverse preparation methods have been developed for the development of nano-sized particles of metal [6]. HME is a continuous manufacturing process that can be easily scaled up [7]. Materials can be thrown into the extruder, moved towards the die and homogeneously blended by rotating screws, and extruded from the die (or an orifice) [8][9][10][11].…”

An update on the contribution of hot-melt extrusion technology to novel drug delivery in the twenty-first century: part I

“…The use of HME for improving the solubility and dissolution rate of poorly water-soluble drugs through dispersion or distribution in suitable carriers is well-established, as reflected by its use in the manufacturing of commercial products on the market (Table 1) [62,63,64]. The different mechanisms used to improve drug solubility are improving wettability, modifying physicochemical properties of API, preventing recrystallization, and stabilizing amorphous formulations [65].…”

“…Various reports on solubility enhancement through HME were discussed in recent reviews [3,52,63], including solid dispersions of tadalafil [67], co-amorphous system of indomethacin/arginine [68], solid crystalline suspensions of efavirenz [69], solid solutions of artesunate [70], and ternary inclusion complexes of itraconazole/cyclodextrin [71]. In this section of this review, we present new reports on HME applications for drug solubility enhancement for the readers' interest.…”