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...

Continuous Crystallization Processes in Pharmaceutical Manufacturing: A Review

09 Jun 2023 | Contributor(s): Orehek, J, Teslic, D, Likozar, B

This scientific paper presents an overview of continuous solution crystallization in the pharmaceutical industry. Since the specific knowledge spectrum of precipitation is very broad, topics covering the following were analyzed and assessed in detail: a comparison between batch and continuous...

Continuous Crystallization with Impurity Complexation and Nanofiltration Recycle

09 Jun 2023 | Contributor(s): Vartak, S, Myerson, AS

For crystal-impurity systems with similar structures and molecular weights, the impurity has a strong tendency to incorporate into the crystal lattice, making it difficult to obtain high purity with a single crystallization or even multiple crystallizations. In such cases, complexation of the...

Continuous direct compression as manufacturing platform for sustained release tablets

09 Jun 2023 | Contributor(s): Vanhoorne, V, Holman, J., Cunningham, C., Kumar, A., Vercruysse, J., De Beer, T., Remon, J. P, Vervaet, C

This study presents a framework for process and product development on a continuous direct compression manufacturing platform. A challenging sustained release formulation with high content of a poorly flowing low density drug was selected. Two HPMC grades were evaluated as matrix former: standard...

Continuous direct compression: Development of an empirical predictive model and challenges regarding PAT implementation

09 Jun 2023 | Contributor(s): Bekaert, B., Van Snick, B., Pandelaere, K., Dhondt, J., Di Pretoro, G., De Beer, T., Vervaet, C., Vanhoorne, V.

In this study, an empirical predictive model was developed based on the quantitative relationships between blend properties, critical quality attributes (CQA) and critical process parameters (CPP) related to blending and tableting. The blend uniformity and API concentration in the tablets were...

Continuous direct tablet compression: effects of impeller rotation rate, total feed rate and drug content on the tablet properties and drug release

09 Jun 2023 | Contributor(s): Jarvinen, Maiju A., Paaso, Janne, Paavola, Marko, Leiviska, Kauko, Juuti, Mikko, Muzzio, Fernando, Jarvinen, Kristiina

Context: Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages. Objective: This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process....

Continuous downstream processing of milled electrospun fibers to tablets monitored by near-infrared and Raman spectroscopy

09 Jun 2023 | Contributor(s): Szabo, E, Zahonyi, PGyurkes, M, Nagy, B, Galata, DL, Madarasz, L, Hirsch, E, Farkas, A, Andersen, SK, Vigh, T, Verreck, G, Csontos, I, Marosi, G, Nagy, ZK

Electrospinning is a technology for manufacture of nano- and micro-sized fibers, which can enhance the dissolution properties of poorly water-soluble drugs. Tableting of electrospun fibers have been demonstrated in several studies, however, continuous manufacturing of tablets have not been...

Continuous end-to-end production of solid drug dosage forms: Coupling flow synthesis and formulation by electrospinning

09 Jun 2023 | Contributor(s): Balogh, Attila, Domokos, András, Farkas, Balázs, Farkas, Attila, Rapi, Zsolt, Kiss, Domokos, Nyiri, Zoltán, Eke, Zsuzsanna, Szarka, Györgyi, Örkényi, Róbert, Mátravölgyi, Béla, Faigl, Ferenc

Based on the concept of continuous manufacturing an end-to-end benchtop device was developed unprecedented for the production of solid drug dosage forms by connecting flow synthesis and formulation via electrospinning (ES). Together with the optimized two-step continuous-flow synthesis of...

Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates

09 Jun 2023 | Contributor(s): Otvos, SB, Kappe, CO

Catalytic enantioselective transformations provide well-established and direct access to stereogenic synthons that are broadly distributed among active pharmaceutical ingredients (APIs). These reactions have been demonstrated to benefit considerably from the merits of continuous processing and...

Comparison of a continuous ring layer wet granulation process with batch high shear and fluidized bed granulation processes

09 Jun 2023 | Contributor(s): Jarvinen, MA, Paavola, M, Poutiainen, S, Itkonen, P, Pasanen, V, Uljas, K, Leiviska, K, Juuti, M, Ketolainen, J, Jarvinen, K

The traditional batch wet granulation processes encounter several challenges, such as problems in the scale-up step, batch-to-batch variability together with the multivariate and difficult to control nature of the process. A continuous wet granulation technique could be a possible solution for...

Complexation-Assisted Continuous Crystallization of Isomeric Systems with Nanofiltration Recycle

09 Jun 2023 | Contributor(s): Vartak, S, Myerson, AS

In API-impurity systems consisting of structural isomers, the impurity has a strong affinity to incorporate into the host crystal owing to their identical molecular weight and similar structure. Conventional successive recrystallization turns out to be an unattractive purification strategy in...

Composite Hydrogels Laden with Crystalline Active Pharmaceutical Ingredients of Controlled Size and Loading

09 Jun 2023 | Contributor(s): Eral, HB, O'Mahony, MShaw, R, Trout, BL, Myerson, AS, Doyle, PS

Efficient control of crystallization and crystal properties still represents a bottleneck in the manufacturing of crystalline materials ranging from pigments to semiconductor particles. In the case of pharmaceutical drug manufacture, current methods for controlling critical crystal properties...

Comprehensive modelling of pharmaceutical solvation energy in different solvents

09 Jun 2023 | Contributor(s): Panwar, A, Shirazian, SSingh, M, Walker, GM

Crystallization is an important processing step in production of active pharmaceutical ingredients (API). This process is used to recover/separate the synthesized APIs for further processing to final solid dosage oral formulations. Control and understanding of crystallization are of great...

Computer Aided Design of Solvent Blends for Hybrid Cooling and Antisolvent Crystallization of Active Pharmaceutical Ingredients

09 Jun 2023 | Contributor(s): Watson, OL, Jonuzaj, SMcGinty, J, Sefcik, J, Galindo, A, Jackson, G, Adjiman, CS

Choosing a solvent and an antisolvent for a new crystallization process is challenging due to the sheer number of possible solvent mixtures and the impact of solvent composition and crystallization temperature on process performance. To facilitate this choice, we present a general computer aided...

Concentration monitoring with near infrared chemical imaging in a tableting press

09 Jun 2023 | Contributor(s): Dalvi, Himmat, Fauteux-Lefebvre, Clémence, Guay, Jean-Maxime, Abatzoglou, Nicolas, Gosselin, Ryan

Monitoring powder potency and homogeneity is important in achieving real-time release testing in a continuous tablet manufacturing operation. If quality related issues are encountered, monitoring powder potency inside a feed frame offers a last opportunity to intervene in the process before...

Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation

09 Jun 2023 | Contributor(s): Kumar, Ashish, Vercruysse, Jurgen, Vanhoorne, Valerie, Toiviainen, Maunu, Panouillot, Pierre-Emmanuel, Juuti, Mikko, Vervaet, Chris, Remon, Jean Paul, Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar

Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution...

Concurrent Antisolvent Electrospraying: A Novel Continuous Crystallization Technique

09 Jun 2023 | Contributor(s): Perge, L, Grols, JSegura, DF, Al-Ani, A, Wilkinson, M, Castro-Dominguez, B

Pharmaceutical co-crystals (CCs) are multicomponent materials that enable the development of novel therapeutic products by enhancing the properties of active pharmaceutical ingredients, such as solubility, permeability and bioavailability. Currently, CCs are a commercial reality; theless, their...

Construction of ultrathin PTMSP/Porous nanoadditives membranes for highly efficient organic solvent nanofiltration (OSN)

09 Jun 2023 | Contributor(s): Liu, Q, Smith, SJDKonstas, K, Ng, D, Zhang, KS, Hill, MR, Xie, ZL

Organic solvent nanofiltration (OSN), also known as solvent resistant nanofiltration (SRNF), has enormous potential for industrial applications. Among the emerging high-performance membrane materials, some have proven challenging to fabricate ultrathin selective layers and at a scale large enough...

Continuous and Scalable Process for the Production of Hollow Crystals of a Poorly Water-Soluble Active Pharmaceutical Ingredient for Dissolution Enhancement and Inhaled Delivery

09 Jun 2023 | Contributor(s): Sheng, F, Chow, PSDong, YC, Heng, D, Lee, SH, Tan, RBH

This study reports a new technique for the manufacture of micron-sized, hollow crystals of a poorly water-soluble pharmaceutical compound, spironolactone, by a continuous and scalable antisolvent precipitation platform called a static mixer. Additives (polyvinylpyrrolidone (PVP) and Tween 80)...