Process Control of Drug Product Continuous Manufacturing Operations - a Study in Operational Simplification and Continuous Improvement

09 Jun 2023 | Contributor(s): Medendorp, Joseph, Shapally, Sreendhar, Vrieze, Derek, Tolton, Kelly

Purpose The purpose of this manuscript is to demonstrate that implementation of gravimetric measurements provides the same assurance of product quality and process control as spectroscopic measurements (1) for control of drug content in a fixed-dose combination (FDC) tablet and (2) for...

Process Analytical Technology for continuous manufacturing of solid-dosage forms

09 Jun 2023 | Contributor(s): Fonteyne, Margot;, Vercrusysse, Jurgen, De Leersnyder, Fien, Van Snick, Bernd, Vervaet, Chris, Remon, Jean, De Beer, Thomas

Currently, pharmaceutical production is making the switch from batch processing towards continuous processing. The quality of intermediate and end products produced by batch processes is assured by off-line testing. It is obvious that off-line tests in analytical laboratories cancel out the...

Process analytical technology for continuous manufacturing tableting processing: A case study

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

The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...

Process Design and Control of a Twin Screw Hot Melt Extrusion for Continuous Pharmaceutical Tamper-Resistant Tablet Production

09 Jun 2023 | Contributor(s): Baronsky-Probst, J., Möltgen, C.-V., Kessler, W., Kessler, R.W.

Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most...

Process analytical technology for continuous manufacturing tableting processing: A case study

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

The use of Near Infrared Spectroscopy (NIRS) as a fast and non-destructive technique was employed for the control and monitoring of the tableting step during a continuous manufacturing process. Two NIRS methods were optimized in order to in-line control the blend uniformity in the tablet feed...

Process analytical technology in continuous manufacturing of a commercial pharmaceutical product

09 Jun 2023 | Contributor(s): Vargas, Jenny, Nielsen, Sarah, Cárdenas, Vanessa, Gonzalez, Anthony, Aymat, Efrain, Almodovar, Elvin, Classe, Gustavo, Colón, Yleana, Sanchez, Eric, Romañach, Rodolfo

The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial...

Process Control of Drug Product Continuous Manufacturing Operations - a Study in Operational Simplification and Continuous Improvement

09 Jun 2023 | Contributor(s): Medendorp, Joseph, Shapally, Sreendhar, Vrieze, Derek, Tolton, Kelly

Purpose The purpose of this manuscript is to demonstrate that implementation of gravimetric measurements provides the same assurance of product quality and process control as spectroscopic measurements (1) for control of drug content in a fixed-dose combination (FDC) tablet and (2) for...

Process Design and Control of a Twin Screw Hot Melt Extrusion for Continuous Pharmaceutical Tamper-Resistant Tablet Production

09 Jun 2023 | Contributor(s): Baronsky-Probst, J., Möltgen, C.-V., Kessler, W., Kessler, R.W.

Hot melt extrusion (HME) is a well-known process within the plastic and food industries that has been utilized for the past several decades and is increasingly accepted by the pharmaceutical industry for continuous manufacturing. For tamper-resistant formulations of e.g. opioids, HME is the most...

Process Design and Optimization for the Continuous Manufacturing of Nevirapine, an Active Pharmaceutical Ingredient for HIV Treatment

09 Jun 2023 | Contributor(s): Diab, S, McQuade, DTGupton, BF, Gerogiorgis, DI

The development of efficient and cost-effective manufacturing routes toward HIV active pharmaceutical ingredients (APIs) is essential to ensure their global and affordable access. Continuous pharmaceutical manufacturing (CPM) is a new production paradigm for the pharmaceutical industry whose...

Process design applied to optimise a directly compressible powder produced via a continuous manufacturing process

09 Jun 2023 | Contributor(s): Gonnissen, Y., Goncalves, S. I. V., De Geest, B. G., Remon, J. P., Vervaet, C.

Manufacturing of 'ready-to-compress' powder mixtures for direct compression was performed by spray drying, without granulation, milling and/or blending steps in between spray drying and compaction. Powder mixtures containing acetaminophen, mannitol, erythritol, maltodextrin, crospovidone,...

Power consumption during oscillatory mixing of pharmaceutical powders

09 Jun 2023 | Contributor(s): Hilden, J, Sullivan, MPolizzi, M, Wade, J, Greer, J, Keeney, M

The blending of powders is a critical step in pharmaceutical drug product manufacturing as it ensures that each dosage unit will contain the same intended fraction of active pharmaceutical ingredient (API). Under-blending thus poses a significant risk to patients where overdose or underdose can...

Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying

09 Jun 2023 | Contributor(s): Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus

Continuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase...

Prediction of quality attributes of continuously produced granules using complementary PAT tools

09 Jun 2023 | Contributor(s): Fonteyne, Margot, Soares, Sandra, Vercruysse, Jurgen, Peeters, Elisabeth, Burggraeve, Anneleen, Vervaet, Chris, Remon, Jean Paul, Sandler, Niklas, De Beer, Thomas

Manufacturers of pharmaceutical solid dosage forms aim for a reduced production time and a shorter‘‘time-to-market.’’ Therefore, continuous manufacturing gains increasing interest in the pharmaceutical industry. For continuous manufacturing, the quality of produced pharmaceuticals should be...

Powder technology in the pharmaceutical industry: the need to catch up fast

09 Jun 2023 | Contributor(s): Fernando J. Muzzio, Troy Shinbrot, Benjamin JGlasser

Pharmaceutical product development and manufacturing, which is largely an exercise in particle technology, is in serious need of technical upgrading. In this article, an overview of the current state of the art is provided, along with a discussion of expected Research Article trends and their...

Power consumption during oscillatory mixing of pharmaceutical powders

09 Jun 2023 | Contributor(s): Hilden, J, Sullivan, MPolizzi, M, Wade, J, Greer, J, Keeney, M

The blending of powders is a critical step in pharmaceutical drug product manufacturing as it ensures that each dosage unit will contain the same intended fraction of active pharmaceutical ingredient (API). Under-blending thus poses a significant risk to patients where overdose or underdose can...

Predicting feeder performance based on material flow properties

09 Jun 2023 | Contributor(s): Yifan Wang, Benjamin J. Glasser, Fernando J. Muzzio 

Purpose: Accurate and consistent delivery of materials by well-designed feeders ensures overall process stability. Importantly, feeding performance is strongly dependent on material flow properties. The purpose of this study is to develop a methodology that identifies predictive correlation...

Predicting film thickness on film coated tablets

09 Jun 2023 | Contributor(s): Rowe, RC

Film thicknesses on film coated tablets have been predicted based on the assumption that the increase in volume of a tablet core after coating is a result of a uniform thickness of polymer coating, i.e. a calculation of the dry volume increase in film coating per unit area of a tablet surface...

Prediction and control of crystal shape distribution in the presence of crystal growth modifiers

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Majumder, Aniruddha, Nagy, Zoltan K

The crystal product quality, functionality and properties such as flow characteristics are greatly influenced by the crystal size and shape distributions. Hence, prediction and control of crystal size and shape distributions are important from the viewpoint of smooth operation and product...

Prediction of quality attributes of continuously produced granules using complementary PAT tools

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Fonteyne, Margot, Soares, Sandra, Vercruysse, Jurgen, Peeters, Elisabeth, Burggraeve, Anneleen, Vervaet, Chris, Remon, Jean Paul, Sandler, Niklas, De Beer, Thomas

Manufacturers of pharmaceutical solid dosage forms aim for a reduced production time and a shorter‘‘time-to-market.’’ Therefore, continuous manufacturing gains increasing interest in the pharmaceutical industry. For continuous manufacturing, the quality of produced pharmaceuticals should be...

Prediction of segregation tendency occurrence in dry particulate pharmaceutical mixtures: Development of a mathematical tool adapted for granular systems application

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Abatzoglou, N;, Simard, JS

Segregation phenomena are of importance in nearly all processes involving dry granular and powder mixtures. The extent of segregation directly influences the eventual rejection of a considerable percentage of the final product in the majority of pharmaceutical processes; among these are those...

Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Pauli, Victoria, Kleinebudde, Peter, Krumme, Markus

Continuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase...

Practical application of roller compaction process modeling

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Reynolds, Gavin, Ingale, Rohit Roberts, Ron Kothari, Sanjeev, Gururajan, Bindhu

Very limited work has been reported on comparing the performance of the roller compaction process at different scales. The majority of the approaches highlighted in the literature discuss the applicability of using confined uniaxial compaction for predicting the performance of the roller...

Predicting Pharmaceutical Particle Size Distributions Using Kernel Mean Embedding

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Van Hauwermeiren, Daan, Stock, Michiel, De Beer, Thomas, Nopens, Ingmar

In the pharmaceutical industry, the transition to continuous manufacturing of solid dosage forms is adopted by more and more companies. For these continuous processes, high-quality process models are needed. In pharmaceutical wet granulation, a unit operation in the ConsiGmaTM-25 continuous...

Prediction of tablet weight variability in continuous manufacturing

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Razavi, Sonia M., Scicolone, James, Snee, Ronald D., Kumar, Ashish, Bertels, Johny, Cappuyns, Philippe, Van Assche, Ivo, Cuitino, Alberto M, Muzzio, Fernando

This paper provides a method for prediction of weight variability of tablets made in rotary tablet presses as a function of material attributes and processing parameters. The goal was to be able to predict whether or not a formulation is suitable for direct compaction continuous manufacturing...

Pharmaceutical spray drying: solid-dose process technology platform for the 21st century

09 Jun 2023 | Peer-reviewed journal | Contributor(s): Snyder, HE

Requirement for precise control of solid-dosage particle properties created with a scalable process technology are continuing to expand in the pharmaceutical industry. Alternate methods of drug delivery, limited active drug substance solubility and the need to improve drug product stability under...