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

09 Jun 2023 | 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 | 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 multivariate raw material property database to facilitate drug product development and enable in-silico design of pharmaceutical dry powder processes

09 Jun 2023 | Contributor(s): Van;Snick, B, Dhondt, JPandelaere, K, Bertels, J, Mertens, R, Klingeleers, D, Di, Pretoro, G, Remon, JP, Vervaet, C, De, Beer, T, Vanhoorne, V

In current study a holistic material characterization approach was proposed and an extensive raw material property database was developed including a wide variety of APIs and excipients with different functionalities. In total 55 different materials were characterized and described by over 100...

A comparative review of multi-rate moving horizon estimation schemes for bioprocess applications

09 Jun 2023 | Contributor(s): Elsheikh, Mohamed, Hille, Rubin Tatulea-Codrean, Alexandru, Kramer, Stefan

Advanced control and monitoring of bioprocesses are dependent on accurate state and parameter information. At the same time, bioprocesses are well known for their time-varying behavior and difficulty of obtaining online measurements of the important process states. The selection and the tuning of...

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

09 Jun 2023 | 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 | 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 | 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 | 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 | 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 | 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 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 design aid for crystal growth engineering

09 Jun 2023 | 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 | 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 | 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 | 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 | 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...

100% visual inspection of tablets produced with continuous direct compression and coating

09 Jun 2023 | Contributor(s): Barimani, Shirin, Sibanc, Rok, Tomazevic, Dejan, Meier, Robin, Kleinebudde, Peter

Visual appearance of tablets is an important property for patients. Since the visual appearance is most strongly influenced by the applied coating, this necessitates a high level of process control and homogeneity in the coating process. In recent years, a number of tablet coaters have been...

3D Printed Reactors for Synthesis of Active Pharmaceutical Ingredients in Continuous Flow

09 Jun 2023 | Contributor(s): Maier, MC, Valotta, AHiebler, K, Soritz, S, Gavric, K, Grabner, B, Gruber-Woelfler, H

Advances in flow chemistry to produce active pharmaceutical ingredients (APIs) require performing reactions in tailor-made equipment as complexity of the planned setups increases. To react quickly and with low costs to these demanding reactions, additive manufacturing, also known as 3D printing,...

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...

7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Ziegler, RE, Desai, BKJee, JA, Gupton, BF, Roper, TD, Jamison, TF

Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5h in sequential...

A brief review on Process Analytical Technology (PAT)

09 Jun 2023 | Peer-reviewed journal | 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 Combined Feed-Forward/Feed-Back Control System for a QbD-Based Continuous Tablet Manufacturing Process

09 Jun 2023 | Peer-reviewed journal | 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 Compact Device for the Integrated Filtration, Drying, and Mechanical Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Capellades, G, Neurohr, CAzad, M, Brancazio, D, Rapp, K, Hammersmith, G, Myerson, AS

Recent changes in the pharmaceutical sector call for the development of novel manufacturing approaches to reduce costs and improve control over product quality. In this area, the development of compact, plug-and-play devices that fit in a continuous manufacturing system has gained interest in...