Continuous manufacturing of co-crystals: challenges and prospects

09 Jun 2023 | Contributor(s): Chavan, Rahul, Thipparaboina, Rajesh, Yadav, Balvant, Shastri, Nalini

The last decade has witnessed extensive growth in the field of co-crystallization for mitigating the solubility and dissolutionrelated issues of poorly soluble drugs. This is largely because co-crystals can modify the physicochemical properties of drugs without any covalent modification in the...

Continuous manufacturing of delta mannitol by cospray drying with PVP

09 Jun 2023 | Contributor(s): Vanhoorne, V., Van Bockstal, P-J., Van Snick, B., Peeters, E., Monteyne, T., Gomes, P., De Beer, T., Remon, J. P., Vervaet, C.

Mannitol is a frequently used diluent in the production of tablets due to its non-hygroscopic character and low drug interaction potential. Although the delta-polymorph of mannitol has superior tabletability in comparison to alpha- and beta-mannitol, the latter are most commonly used because...

Continuous manufacturing of drug substance and small molecules: process and equipment view

09 Jun 2023 | Contributor(s): Yazdanpanah, Nima

The continuous manufacturing of pharmaceutical compounds and fine chemicals is in high interest for the industry due to significant technical, quality, and economical advantages. This manufacturing method has its own challenges. Beside the more efficient, safer, and greener synthesis rout, a new...

Continuous Manufacturing of Drug Substances and Drug Products

09 Jun 2023

Guideline gives information and requirements for the production of API in pharmaceutical continuous manufactring processes.

Continuous Manufacturing of High Quality Pharmaceutical Cocrystals Integrated with Process Analytical Tools for In-Line Process Control

09 Jun 2023 | Contributor(s): Moradiya, Hiren G., Islam, Muhammad, Scoutaris, Nikolaos, Halsey, Sheelagh, Chowdhry, Babur Z., Douroumis, Dennis

A continuous manufacturing process for pharmaceutical indomethacin saccharine cocrystals was achieved by extrusion processing with high throughput. Down-stream milling and blending of the extrudates was followed by feeding the formulated cocrystals in a capsule-filling machine. By applying a...

Continuous Manufacturing of Ketoprofen Delayed Release Pellets Using Melt Extrusion Technology: Application of QbD Design Space, Inline Near Infrared, and Inline Pellet Size Analysis

09 Jun 2023 | Contributor(s): Vo, Anh, Kutz, Gerd, He, Herman, Narala, Sagar, Bandari, Suresh, Repka, Michael A.

Delayed-release dosage forms are mainly manufactured as batch processes and include coated tablets, pellets, or particles with gastric resistant polymers. Authors propose a novel approach using the hot-melt extrusion technique to prepare delayed release dosage forms via a continuous manufacturing...

Continuous manufacturing of tablets with PROMIS-line. Introduction and case studies from continuous feeding, blending and tableting

09 Jun 2023 | Contributor(s): Simonaho, Simo-Pekka, Ketolainena, Jarkko, Ervasti, Tuomas, Toiviaine, Maunu, Korhonen, Ossi

Drug manufacturing technology is in the midst ofmodernization and continuousmanufacturing of drug products is especially the focus of great interest. The adoption of new manufacturing approaches requires extensive cooperation between industry, regulatory bodies, academics and equipment...

Continuous Manufacturing Process Development from Lab to Market, Role of Digital Tools

09 Jun 2023 | Contributor(s): Yazdanpanah, Nima

The continuous manufacturing of pharmaceutical compounds and fine chemicals is in high interest for the industry due to significant technical, quality, and economical advantages. Beside the more efficient, safer, and greener synthesis route, a new process design paradigm and equipment selection...

Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study

09 Jun 2023 | Contributor(s): Roggo, Yves, Pauli, Victoria, Jelsch, Morgane, Pellegatti, Laurent, Elbaz, Frantz, Ensslin, Simon, Kleinebudde, Peter, Krumme, Markus

The most prevalent pharmaceutical dosage forms at present are granular solids in the form of oral tablets and capsules. While effective in releasing drug rapidly upon contact with gastrointestinal fluid, their manufacture, which relies on particulate processing, is fraught with difficulties...

Continuous manufacturing technologies in upstream pharmaceutical supply chains: Combining engineering and managerial criteria

09 Jun 2023 | Contributor(s): Aulakh, PK, Settanni, E, Srai, JS

The COVID-19 pandemic exposed vulnerabilities in upstream pharmaceutical supply chains (PSC). One is that the global supply of active pharmaceutical ingredients (APIs) is overly dependent on few locations and large-scale batch manufacturing. Regulators hope to enable more dependable location...

Continuous manufacturing of pharmaceuticals

09 Jun 2023 | Contributor(s): Johannes Khinast, Jukka Rantanen

A comprehensive look at existing technologies and processes for continuous manufacturing of pharmaceuticals.As rising costs outpace new drug development, the pharmaceutical industry has come under intense pressure to improve the efficiency of its manufacturing processes. Continuous process...

Continuous Flow C-Glycosylation via Metal-Halogen Exchange: Process Understanding and Improvements toward Efficient Manufacturing of Remdesivir

09 Jun 2023 | Contributor(s): von;Keutz, T, Williams, JD, Kappe, CO

As remdesivir is the first approved treatment for COVID-19 (SARS-CoV-2), its production is likely to be of vital importance in the near future. Continuous flow processing has been demonstrated as a key technology in the manufacturing of highvolume active pharmaceutical ingredients and is...

Continuous flow technology vs. the batch-by-batch approach to produce pharmaceutical compounds

09 Jun 2023 | Contributor(s): Cole, KP, Johnson, MD

Introduction: For the manufacture of small molecule drugs, many pharmaceutical innovator companies have recently invested in continuous processing, which can offer significant technical and economic advantages over traditional batch methodology. This Expert Review will describe the reasons for...

Continuous flow upgrading of glycerol toward oxiranes and active pharmaceutical ingredients thereof

09 Jun 2023 | Contributor(s): Morodo, R, Gerardy, RPetit, G, Monbaliu, JCM

A robust continuous flow procedure for the transformation of bio-based glycerol into high value-added oxiranes (epichlorohydrin and glycidol) is presented. The flow procedure features a central hydrochlorination/dechlorination sequence and provides economically and environmentally favorable...

Continuous granulation in the pharmaceutical industry

09 Jun 2023 | Contributor(s): Vervaet, C, Remon, JP

Traditionally the manufacturing of pharmaceutical dosage forms has been a batch-wise process and continuous processes have limited applications in a pharmaceutical manufacturing plant. However, several factors (reduction of cost, improved process efficiency, optimal use of equipment, flexibility...

Continuous Heterogeneous Crystallization on Excipient Surfaces

09 Jun 2023 | Contributor(s): Yazdanpanah, Nimaa, Testa, Christopher J., Perala, Siva R. K., Jensen, Keith D., Braatz, Richard D., Myerson, Allan S., Trout, Bernhardt L.

A novel continuous heterogeneous crystallization process is, developed in which the active pharmaceutical ingredient (API) is crystallized directly on the surface of an excipient within the crystallizer. The produet is subsequently dried and formed into tablets without the need for complex...

Continuous integrated filtration, washing and drying of aspirin: digital design of a novel intensified unit

09 Jun 2023 | Contributor(s): Destro, F, Wang, VAbdi, M, Feng, X, Wood, E, Coleman, S, Firth, P, Barton, A, Barolo, M, Nagy, ZK

Within the recent modernization of pharmaceutical manufacturing, an important milestone consists in developing enabling technologies for end-to-end continuous production of drug products. Continuous filtration, washing and drying of active pharmaceutical ingredients from mother liquors in...

Continuous manufacture of polymeric cellular dosage forms

09 Jun 2023 | Contributor(s): Blaesi, Aron H, Saka, Nannaji

The most prevalent pharmaceutical dosage forms at present are granular solids in the form of oral tablets and capsules. While effective in releasing drug rapidly upon contact with gastrointestinal fluid, their manufacture, which relies on particulate processing, is fraught with difficulties...

Continuous manufacturing – the Green Chemistry promise?

09 Jun 2023 | Contributor(s): Klavs F. Jensen

Continuous manufacturing and Green Chemistry, are two promising approaches to synthesis with underutilized potential that are gaining traction by the wider pharmaceutical community. We review Green Chemistry advances resulting when transitioning to continuous manufacturing with focus on Green...

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing

09 Jun 2023 | Contributor(s): Burcham, Christopher L., Florence, Alastair J., Johnson, Martin D.

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new...

Continuous manufacturing of a pharmaceutical cream: Investigating continuous powder dispersing and residence time distribution (RTD)

09 Jun 2023 | Contributor(s): Bostijn, N, Van, Renterghem, JVanbillemont, B, Dhondt, W, Vervaet, C, De;Beer, T

Recently, an innovative continuous manufacturing technology for a pharmaceutical oral suspension was proposed, based on two consecutive mixing units. A limitation of this technology is the need to dissolve or disperse powder-based raw materials in a liquid via a batch step before continuous...

Continuous Manufacturing of a Polymer Stabilized Emulsion Monitored with Process Analytical Technology

09 Jun 2023 | Contributor(s): Qwist, PK, Sander, CBostijn, N, Jessen, V, Rantanen, J, de;Beer, T

Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process...

Continuous Crystallization of Aliskiren Hemifumarate

09 Jun 2023 | Contributor(s): Quon, JL, Zhang, HAlvarez, A, Evans, J, Myerson, AS, Trout, BL

Active ingredients in most pharmaceutical products are complex organic molecules that require crystallization as a purification and isolation step that results in a pure product at a high process yield. Knowledge of the operating conditions required to obtain crystals with the desired crystal...

Continuous Crystallization of Paracetamol (Acetaminophen) Form II: Selective Access to a Metastable Solid Form

09 Jun 2023 | Contributor(s): Agnew, LR, McGlone, TWheatcroft, HP, Robertson, A, Parsons, AR, Wilson, CC

The first continuous crystallization of a metastable polymorphic form of an active pharmaceutical ingredient is reported. Paracetamol form II, which displays enhanced solubility and compressibility in comparison to the stable form I, has been successfully crystallized in two continuous platforms:...

Continuous crystallization of pharmaceuticals using a continuous oscillatory baffled crystallizer

09 Jun 2023 | Contributor(s): Lawton, Simon, Steele, Gerry Shering, Phil Zhao, Lihua, Laird, Ian, Ni,, Xiong Wei

In this paper, we report an investigation into the continuous crystallization of a model active pharmaceutical ingredient (API) using a continuous oscillatory baffled crystallizer (COBC). The results show that continuous crystallization offers significant advantages in terms of process, operation...