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...

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 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 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 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 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...

A Framework for Representative Sampling for NIR Analysis – Theory of Sampling (TOS)

09 Jun 2023 | Contributor(s): Esbensen, Kim H, Ciurczak, Emil W., Igne, Benoît, Workman, Jr.,Jerome, Burns, Donald A., Romañach, Rodolfo J.

This chapter deals with all critical steps before near-infrared spectroscopy (NIR) analysis, irrespective of whether the total sampling error contribution is large, intermediate, or small – all cases can be treated identically, including the widespread sensor-based solutions from the...

A framework of hybrid model development with identification of plant-model mismatch

09 Jun 2023 | Contributor(s): Chen, Yingjie, Ierapetritou, Marianthi

Abstract Hybrid modeling has attracted increasing attention in order to take advantage of the additional data to improve process understanding. Current practice often adopts mechanistic models to predict process behaviors. These mechanistic models are based on physical understandings and...

A hybrid model for multipoint real time potency observation in continuous direct compression manufacturing operations

09 Jun 2023 | Contributor(s): Gallo-Molina, Juan Pablo, Cogoni, Giuseppe, Peeters, Elisabeth, Rao Ambati, Seshagiri, Nopens, Ingmar

The ongoing transition from batch to continuous manufacturing offers both challenges and opportunities in the field of oral solid dosage form production. In turn, Process Analytical Technology (PAT) offers a path towards the successful deployment of continuous tablet manufacturing in rotary...

A hybrid model for multipoint real time potency observation in continuous direct compression manufacturing operations

09 Jun 2023 | Contributor(s): Gallo-Molina, Juan Pablo, Cogoni, Giuseppe, Peeters, Elisabeth, Rao Ambati, Seshagiri, Nopens, Ingmar

The ongoing transition from batch to continuous manufacturing offers both challenges and opportunities in the field of oral solid dosage form production. In turn, Process Analytical Technology (PAT) offers a path towards the successful deployment of continuous tablet manufacturing in rotary...

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

09 Jun 2023 | 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 MPC-PID Control System Design for the Continuous Purification and Processing of Active Pharmaceutical Ingredients

09 Jun 2023 | 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 | 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 hybrid NIR-soft sensor method for real time in-process control during continuous direct compression manufacturing operations

09 Jun 2023 | Contributor(s): Cogoni, Giuseppe, Husain, Anas, Alam, Md Anik, Liu, Yang Angela, Kamyar, Reza

Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet...

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

09 Jun 2023 | 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 model-based framework for design and analysis of PAT systems

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

A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction

03 Jun 2024 | Peer-reviewed journal | Contributor(s): Hikaru G. Jolliffe, Martin Prostredny, Carlota Mendez Torrecillas, Ecaterina Bordos, Collette Tierney, Ebenezer Ojo, Richard Elkes, Gavin Reynolds, Yunfei Li Song, Bernhard Meir, Sara Fathollahi, John Robertson

Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body...

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 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...