3D printing and continuous flow chemistry technology to advance pharmaceutical manufacturing in developing countries

09 Jun 2023 | Contributor(s): Sagandira, CR, Siyawamwaya, M, Watts, P

The realization of a downward spiralling of diseases in developing countries requires them to become self-sufficient in pharmaceutical products. One of the ways to meet this need is by boosting the local production of active pharmaceutical ingredients and embracing enabling technologies. Both 3D...

A brief review on Process Analytical Technology (PAT)

09 Jun 2023 | Contributor(s): Mali, Akash, Jagtap, Monali, Karekar, P., Maruska, A

Process analytical technology (PAT) has been defined as a mechanism to design, analyze and control pharmaceutical manufacturing processes through measurement of critical process parameters which affect critical quality attributes. PAT checks the quality of raw material attributes both physically...

A Co-Processed API Approach for a Shear Sensitive Compound Affording Improved Chemical Stability and Streamlined Drug Product Processing

09 Jun 2023 | Contributor(s): Schenck, L, Neri, CJia, XJ, Schafer, W, Axnanda, S, Canfield, N, Li, F, Shah, V

The physical properties of active pharmaceutical ingredients (API) are critical to both drug substance (DS) isolation and drying operations, as well as streamlined drug product (DP) processing and the quality of final dosage units. High aspect ratio, low bulk density, API 'needles' in particular...

A Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process

09 Jun 2023 | Contributor(s): Singh, Ravendra, Muzzio, Fernando J, Ierapetritou, Marianthi, Ramachandran, Rohit

Continuous pharmaceutical manufacturing together with PAT (Process Analytical Technology) provides a suitable platform for automatic control of the end product quality as desired by QbD (quality by design)-based efficient manufacturing. The precise control of the quality of the pharmaceutical...

A Comparison Between Lab-Scale and Hot-Melt-Extruder-Based Anti-inflammatory Ointment Manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Thakkar, R, Ashour, EAShukla, A, Wang, R, Chambliss, WG, Bandari, S, Murthy, N, Repka, MA

Hot-melt extrusion (HME) has been extensively investigated for continuous manufacturing of amorphous solid dispersions, to improve the solubility of poorly water-soluble drug substances, impart abuse deterrence to controlled substances, taste masking for pediatric and geriatric formulations and...

A comprehensive analysis and optimization of continuous twin-screw granulation processes via sequential experimentation strategy

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Meng, Wei, Rao, Kallakuri Suparna, Snee, Ronald D., Ramachandran, Rohit., Muzzio, Fernando J

Nowadays twin-screw granulation has been emerging as an attractive continuous wet granulation technique. This study was geared towards better process design and understanding with emphasis on bridging the knowledge gap between input and output variables by employing sequential experimentation...

A comprehensive overview of extended release oral dosage forms manufactured through hot melt extrusion and its combination with 3D printing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Nashed, Nour, Lam, Matthew, Nokhodchi, Ali

Oral dosage formulations are considered to be the most convenient pharmaceutical dosage forms for almost all ages because of their simplicity and non-invasive administration compared to other dosage forms. To improve therapeutic efficacy and avoid frequent daily doses, extending drug release...

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Gambacorta, G, Sharley, JS, Baxendale, IR

Due to their intrinsic physical properties, which includes being able to perform as volatile liquids at room and biological temperatures, fragrance ingredients/intermediates make ideal candidates for continuous-flow manufacturing. This review highlights the potential crossover between a...

A continuous manufacturing concept for a pharmaceutical oral suspension

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bostijn, N, Van, Renterghem, JDhondt, W, Vervaet, C, De;Beer, T

The aim of this study was to investigate the applicability of an innovative continuous manufacturing system for semi-solid and liquid pharmaceutical formulations. A commercially available pharmaceutical oral suspension was selected as model formulation. Premixes of the raw materials were dosed...

A Continuous Operation Concept for a Rotary Tablet Press Using Mass Flow Operating Points

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Martinetz, Michael Christian, Rehrl, Jakob Aigner, Isabella Sacher, Stephan, Khinast, Johannes

Abstract In a continuous pharmaceutical manufacturing line the rotary tablet press was viewed as the master of control concept and defined the mass flow through the entire process. According to a conventional control concept, missing mass flow from an upstream unit operation leads to a shutdown...

A design aid for crystal growth engineering

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Li, Jinjin, Tilbury, Carl J. Kim, Seung Ha, Doherty, Michael F.

With the highly competitive development of chemical and pharmaceutical industries, mastering crystal growth is becoming increasingly necessary. Modern industrial manufacturers place high importance on the ability to grow crystals with a specific habit using tailored operating conditions. A...

A Digital Twin for Process Optimisation in Pharmaceutical Manufacturing

09 Jun 2023 | Chapter Book | Contributor(s): Gerogiorgis, Dimitrios I., Castro-Rodriguez, Daniel

Organic synthesis is a critical step in producing any Active Pharmaceutical Ingredient (API): it encompasses a series of organic (mostly catalytic) reactions and separations, whose purpose is to arrive at a solution of a target molecule, which must then undergo crystallisation for purification,...

A fast moving horizon estimation algorithm based on nonlinear programming sensitivity

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Zavala, Victor M, Laird, Carl D, Biegler, Lorenz T

Moving horizon estimation (MHE) is an efficient optimization-based strategy for state estimation. Despite the attractiveness of this method, its application in industrial settings has been rather limited. This has been mainly due to the difficulty to solve, in real-time, the associated dynamic...

A flowsheet model for the development of a continuous process for pharmaceutical tablets: An industrial perspective

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Garcia-Munoz, Salvador, Butterbaugh, Adam Leavesley, Ian Manley, Leo Francis, Slade, David, Bermingham, Sean

A dynamic model of a continuous direct compression process for pharmaceutical tablets is presented. The objective is to assess the impact of the variability from the feeder system on the concentration of drug in the powder in the feed frame of a tablet press. The model is based on principles of...

A flowsheet model for the development of a continuous process for pharmaceutical tablets: An industrial perspective

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Garcia-Munoz, Salvador, Butterbaugh, Adam Leavesley, Ian Manley, Leo Francis, Slade, David, Bermingham, Sean

A dynamic model of a continuous direct compression process for pharmaceutical tablets is presented. The objective is to assess the impact of the variability from the feeder system on the concentration of drug in the powder in the feed frame of a tablet press. The model is based on principles of...

A framework for model reliability and estimability analysis of crystallization processes with multi-impurity multi-dimensional population balance models

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Fysikopoulos, D, Benyahia, B Borsos, A Nagy, Z K, Rielly, C D

The development of reliable mathematical models for crystallization processes may be very challenging due the complexity of the underlying phenomena, the inherent Population Balance Models (PBMs) and the large number of parameters that need to be identified from experimental data. Due to the poor...

A Hybrid MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, M, Singh, R, Ramachandran, R

In this work, a hybrid MPC (model predictive control)-PID (proportional-integral-derivative) control system has been designed for the continuous purification and processing framework of active pharmaceutical ingredients (APIs). The specific unit operations associated with the purification and...

A hybrid neural network-first principles approach to process modeling

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Psichogios, Dimitris C., Ungar, Lyle H.

A hybrid neural network‐first principles modeling scheme is developed and used to model a fedbatch bioreactor. The hybrid model combines a partial first principles model, which incorporates the available prior knowledge about the process being modeled, with a neural network which...

A large-scale experimental comparison of batch and continuous technologies in pharmaceutical tablet manufacturing using ethenzamide

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Matsunami, Kensaku, Nagato, Takuya, Hasegawa, Koji, Sugiyama, Hirokazu

This paper compares batch and continuous technologies in terms of product quality and process performance in pharmaceutical tablet manufacturing using ethenzamide as the active pharmaceutical ingredient. Batch and continuous processes using wet granulation were investigated by performing...

A model-based framework for design and analysis of PAT systems

09 Jun 2023 | Workshop | Contributor(s): Gani, Rafiqul, Singh, Ravendra, Gernaey, Krist

A multi-scale hybrid CFD-DEM-PBM description of a fluid-bed granulation process

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Sen, Maitraye, Barrasso, Dana Singh, Ravendra, Ramachandran, Rohit

In this study, a hybrid multi-scale model has been developed for a continuous fluid bed wet granulation process by dynamically coupling computational fluid dynamics (CFD) with a discrete element model (DEM) and population balance model (PBM). In this process, the granules are formed by spraying...

A multivariate approach to predict the volumetric and gravimetric feeding behavior of a low feed rate feeder based on raw material properties

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Bostijn, N, Dhondt, J, Ryckaert, A, Szabo, E, Dhondt, W, Van Snick, B, Vanhoorne, V, Vervaet, C, De Beer, T

In this study, the volumetric and gravimetric feeding behavior of 15 pharmaceutical powders on a low feed rate feeder was correlated with their material properties through a multivariate approach. The powders under investigation differ substantially in terms of material properties, making the...

A New Software Framework for Implementing Crystal Growth Models to Materials of Any Crystallographic Complexity

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Zhao, Yongsheng, Tilbury, Carl J. Landis, Steven Sun, Yuanyuan, Li, Jinjin, Zhu, Peng, Doherty, Michael F.

To continue the realization of new therapeutics, a more diverse range of solid forms is being considered. Synthetic modalities are broadening beyond simple organic molecules to more complicated structures, including organic salts, cocrystals, and solvates. As in all crystalline applications,...

A NIR-Based Study of Desorption Kinetics during Continuous Spin Freeze-Drying

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Leys, Laurens, Nuytten, Gust, Lammens, Joris, Van Bockstal, Pieter-Jan, Corver, Jos, Vervaet, Chris, De Beer, Thomas

The pharmaceutical industry is progressing toward the development of more continuous manufacturing techniques. At the same time, the industry is striving toward more process understanding and improved process control, which requires the implementation of process analytical technology tools (PAT)....