Coupling hot melt extrusion and fused deposition modeling: Critical properties for successful performance

09 Jun 2023 | Contributor(s): Bandari, Suresh, Nyavanandi, Dinesha, Dumpa, Nagireddy, Repka, Michael A.

Interest in 3D printing for pharmaceutical applications has increased in recent years. Compared to other 3D printing techniques, hot melt extrusion (HME)-based fused deposition modeling (FDM) 3D printing has been the most extensively investigated for patient-focused dosage. HME technology can be...

Cross-Pharma Collaboration for the Development of a Simulation Tool for the Model-Based Digital Design of Pharmaceutical Crystallization Processes (CrySiV)

09 Jun 2023 | Contributor(s): Szilagyi, Botond, Wu, Wei Lee Eren, Ayse Mackey, Jaron, Kshirsagar, Shivani, Szilagyi, Emoke, Ostergaard, Iben, Qu, Haiyan, Sinha, Kushal, Mlinar, Laurie, Pohlman, Daniel, Chen, Jie, Nere, Nandkishor, Boukerche, Moussa, Korde, Akshay, Ellis, Ryan, Lovette, Michael, Black, Simon, Jawor-Baczynska, Anna, Li, Huayu, Yang, Bing Shiou, Irdam, Erwin, Patience, Daniel, McKeown, Rahn, Ketchum, Megan, Green, Daniel A., Reddy, Venkata Ramana, Polster, Christopher, Burcham, Christopher, Jarmer, Daniel, Merritt, Jeremy Miles, Cote, Aaron, Sirota, Eric, Codan, Lorenzo, Schoell, Jochen, Liu, Yiqing Claire, Girard, Kevin P., Kulkarni, Samir A., Yang, Yihui, Quon, Justin L., Nagy, Zoltan K.

Precompetitive collaborations on new enabling technologies for Research Article and development are becoming popular among pharmaceutical companies. The Enabling Technologies Consortium (ETC), a precompetitive collaboration of leading innovative pharmaceutical companies, identifies and executes...

Crystal and Particle Engineering Strategies for Improving Powder Compression and Flow Properties to Enable Continuous Tablet Manufacturing by Direct Compression

09 Jun 2023 | Contributor(s): Chattoraj, Sayantan, Sun, Changquan Calvin

Continuous manufacturing of tablets has many advantages, including batch size flexibility, demand-adaptive scale up or scale down, consistent product quality, small operational foot print, and increased manufacturing efficiency. Simplicity makes direct compression the most suitable process for...

Crystal Population Balance Formulation and Solution Methods: A Review

09 Jun 2023 | Contributor(s): Omar, Hecham M., Rohani, Sohrab

Crystallization is an important part of many chemical industries. Efforts are being invested to improve the performance of the crystallization process by designing novel crystallizers. An important aspect in the development of new crystallizers is the ability to describe the behavior of such...

Crystal shape and size control using a plug flow crystallization configuration

09 Jun 2023 | Contributor(s): Sang-Il Kwon, Joseph, Nayhouse, Michael Orkoulas, Gerassimos

This work focuses on modeling and control of a continuous plug flow crystallizer (PFC) used to produce tetragonal hen-egg-white (HEW) lysozyme crystals and proposes an optimization-based control scheme to produce crystals with desired size and shape distributions in the presence of disturbances....

Crystal Size Control in a Continuous Tubular Crystallizer

09 Jun 2023 | Contributor(s): Besenhard, Maximilian O., Neugebauer, Peter Ho, Cheng-Da, Khinast, Johannes G.

This paper describes a simple model-free (i.e., empirical) control strategy for crystal size tuning in a continuously operated tubular crystallizer. The crystallizer is designed for a seeded cooling crystallization process and acetylsalicylic acid crystallization from an ethanol solution was used...

Crystallisation and physicochemical property characterisation of conformationally-locked co-crystals of fenamic acid derivatives

09 Jun 2023 | Contributor(s): Wittering, KE, Agnew, LRKlapwijk, AR, Robertson, K, Cousen, AJP, Cruickshank, DL, Wilson, CC

Polymorphism in drug compounds can cause significant problems for industrial-scale production and so a method for restricting the conformational freedom of the target compound whilst retaining desired chemical properties is highly beneficial to the pharmaceutical industry. Co-crystallisation is...

Crystallization of Cyclosporine in a Multistage Continuous MSMPR Crystallizer

09 Jun 2023 | Contributor(s): Alvarez, Alejandro J., Singh, Aniruddh, Myerson, Allan S.

Crystallization processes can be batch or continuous. Potential advantages such as operating at steady state, small equipment size (relative to batch), and ability to recycle are encouraging the pharmaceutical industry to investigate continuous processes. In this work, a continuous cooling...

Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century

09 Jun 2023 | Contributor(s): Tiwari, RV, Patil, H, Repka, MA

Introduction: Hot-melt extrusion (HME) technology is applied successfully in the plastic, rubber and food industry. HME has also emerged as an important technology for drug delivery applications in pharmaceutical Research Article and manufacturing because of its process automation and low-cost...

Control of a system of loss-in-weight feeders for drug product continuous manufacturing

09 Jun 2023 | Contributor(s): Hanson, Joshua

Loss-in-weight (LIW) feeders are used to dispense individual materials to the downstream unit operations in continuous drug product manufacturing processes. The purpose of this work was to identify potential material feeding failure modes and demonstrate how a ratio control loop can be used to...

Control of Batch and Continuous Crystallization Processes using Reinforcement Learning

09 Jun 2023 | Contributor(s): Benyahia, Brahim, Anandan, Paul Danny Rielly, Chris Türkay, Metin, Gani, Rafiqul

In crystallization processes, the control of particle size distribution, shape and purity are crucial to achieve the targeted critical quality attributes of the final drug product and meet the pharmaceutical regulatory requirements. This work presents novel optimal trajectory tracking control...

Control of Drug-Excipient Particle Attributes with Droplet Microfluidic-based Extractive Solidification Enables Improved Powder Rheology

09 Jun 2023 | Contributor(s): Ng, DZL, Nelson, AZWard, G, Lai, D, Doyle, PS, Khan, SA

Purpose Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients(APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the...

Control of Pharmaceutical Cocrystal Polymorphism on Various Scales by Mechanochemistry: Transfer from the Laboratory Batch to the Large-Scale Extrusion Processing

09 Jun 2023 | Contributor(s): Stolar, T, Lukin, STireli, M, Sovic, I, Karadeniz, B, Kerekovic, I, Matijasic, G, Gretic, M, Katancic, Z, Dejanovic, I, di, Michiel, M, Halasz, I, Uzarevic, K

We demonstrate a controllable mechanochemical synthesis of cocrystal polymorphs of ascorbic acid (vitamin C) and nicotinamide (vitamin B3) on different scales and without using bulk solvents. Next to the previously described polymorph of the 1:1 cocrystal, which is one of the first cocrystals...

Control of process operations and monitoring of product qualities through generic model-based in batch cooling crystallization

09 Jun 2023 | Contributor(s): Samad, Noor Asma Fazli Abdul, Singh, Ravendra Sin, Gürkan Gernaey, Krist V, Gani, Rafiqul

A generic model-based framework has been developed for crystallization processes, with applications aiming at the control of process operations and the monitoring of product quality. This generic model-based framework allows the systematic development of a wide range of crystallization models for...

CONTROL OF THE CONTINUOUS VIBRATION FLUIDIZED-BED DRYING BY MEASUREMENT OF THE RELATIVE GRANULATION HUMIDITY

09 Jun 2023 | Contributor(s): FUCHS, G, PATT, L, HABERSTROH, A

This article describes a method to measure the relative granulation humidity in the pharmaceutical production. The method is employed as on-line process controll for monitoring the continuous fluidized-bed drying process. The dryer settings are adjusted according to the relative humidity...

Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors

09 Jun 2023 | Contributor(s): Rehrl, J, Karttunen, APNicolai, N, Hormann, T, Horn, M, Korhonen, O, Nopens, I, De, Beer, T, Khinast, JG

One major advantage of continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the...

Control strategy and methods for continuous direct compression processes

09 Jun 2023 | Contributor(s): Suzuki, Yasuhiro, Sugiyama, Hirokazu, Kano, Manabu, Shimono, Ryutaro, Shimada, Gosuke, Furukawa, Ryoichi, Mano, Eichi, Motoyama, Keiichi, Koide, Tatsuo, Matsui, Yasuhiro, Kurasaki, Kazuki, Takayama, Issei, Hikage, Shunin, Katori, Noriko, Kikuchi, Masahiko, Sakai, Hiroshi, Matsuda, Yoshihiro

We presented a control strategy for tablet manufacturing processes based on continuous direct compression. The work was conducted by the experts of pharmaceutical companies, machine suppliers, academia, and regulatory authority in Japan. Among different items in the process, the component ratio...

Control strategy definition for a drug product continuous wet granulation process: Industrial case study

09 Jun 2023 | Contributor(s): Chavez, Pierre-François, Stauffer, Fanny, Eeckman, Frédéric, Bostijn, Nils, Didion, David, Schaefer, Cédric, Yang, Hong, El Aalamat, Yousef, Lories, Xavier, Warman, Martin, Mathieu, Benoit, Mantanus, Jérôme

This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with...

Continuous twin screw granulation: Impact of binder addition method and surfactants on granulation of a high-dosed, poorly soluble API

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite the recent commercialization of several drug products manufactured through continuous manufacturing techniques, knowledge on the formulation aspect of these techniques, such as twin screw wet granulation, is still rather limited. Previous Research Article identified lactose/MCC/HPMC as a...

Continuous twin screw granulation: Impact of microcrystalline cellulose batch-to-batch variability during granulation and drying - A QbD approach

09 Jun 2023 | Contributor(s): Portier, Christoph, Vigh, Tamas, Di Pretoro, Giustino, Leys, Jan, Klingeleers, Didier, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

Despite significant advances in the Research Article domain of continuous twin screw granulation, limited information is currently available on the impact of raw material properties, especially considering batch-to-batch variability. The importance of raw material variability and subsequent...

Continuous twin screw granulation: Influence of process and formulation variables on granule quality attributes of model formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, Pandelaere, Kenny, Delaet, Urbain, Vigh, Tamas, Kumar, Ashish, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, continuous manufacturing techniques, such as twin screw wet granulation, have gained significant momentum. Due to the large diversity of the (model) formulations and equipment, it is often difficult to generalize conclusions about the importance of process settings. As only...

Continuous twin screw granulation: Influence of process variables on granule and tablet quality

09 Jun 2023 | Contributor(s): Vercruysse, J., Diaz, D. Cordoba, Peeters, E., Fonteyne, M., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Veryaet, C.

The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, alpha-lactose monohydrate...

Continuous twin screw granulation: Robustness of lactose/MCC-based formulations

09 Jun 2023 | Contributor(s): Portier, Christoph, De Vriendt, Charlotte, Vigh, Tamas, Di Pretoro, Giustino, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

In recent years, significant progress has been made in the field of continuous twin screw granulation. However, only limited knowledge is currently available on the impact of active pharmaceutical ingredient (API) properties on granule quality and processability. In this study, the response...

Continuous Twin Screw Wet Granulation and Drying - Control Strategy for Drug Product Manufacturing

09 Jun 2023 | Contributor(s): Dahlgren, Gabriella, Tajarobi, Pirjo, Simone, Eric, Ricart, Brendon, Melnick, Jason, Puri, Vibha, Stanton, Courtney, Bajwa, Gurjit

The use of continuous manufacturing has been increasing within the pharmaceutical industry over the last few years. Continuous direct compression has been the focus of publications on the topic to date. The use of wet granulation can improve segregation resistance, uniformity, enhance density,...

Continuous twin screw wet granulation: The combined effect of process parameters on residence time, particle size, and granule morphology

09 Jun 2023 | Contributor(s): Shirazian, Saeed, Zeglinski, Jacek, Darwish, Shaza, Kuhs, Manuel, Albadarin, Ahmad B., Croker, Denise M., Walker, Gavin M.

In this study, a set of 24 experiments was designed to understand the combined effect of different process parameters, i.e. material feed rate, liquid-to-solid (L/S) ratio, screw speed, and screw configuration on the residence time distribution, granule morphology, and particle size distribution...