Grey-Box Approach for the Prediction of Variable Residence Time Distribution in Continuous Pharmaceutical Manufacturing

09 Jun 2023 | Contributor(s): Elkhashap, A, Meier, R, Stenger, D, Abel, D

Axial dispersion models are used for the prediction of residence time distribution (RTD) of the flow occurring in various processes. Such models are essential for the understanding of the flow dynamics allowing monitoring, control and material tracing specially in the scope of continuous...

Guidance for Industry PAT - A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance

09 Jun 2023

This guidance is intended to describe a regulatory framework (Process Analytical Technology, PAT) that will encourage the voluntary development and implementation of innovative pharmaceutical development, manufacturing, and quality assurance. Working with existing regulations, the Agency has...

Habit Modification of the Active Pharmaceutical Ingredient Lovastatin Through a Predictive Solvent Selection Approach

09 Jun 2023 | Contributor(s): Turner, TD, Hatcher, LEWilson, CC, Roberts, KJ

An analysis of the important intermolecular interactions of the active pharmaceutical ingredient lovastatin which contribute to the surface chemistry and attachment energy morphology is presented. The analysis is supported by a recent redetermination of the single-crystal structure (orthorhombic...

Heat Transfer Evaluation During Twin-Screw Wet Granulation in View of Detailed Process Understanding

09 Jun 2023 | Contributor(s): Stauffer, Fanny, Ryckaert, Alexander, Van Hauwermeiren, Daan, Funke, Adrian, Djuric, Dejan, Nopens, Ingmar, De Beer, Thomas

During the last decade, the pharmaceutical industry has shown a growing interest in continuous twin-screw granulation (TSG). Despite flourishing literature on TSG, limited studies focused on fundamental process understanding on its mechanisms. In current study, granule quality attributes along...

Heating under High-Frequency Inductive Conditions: Application to the Continuous Synthesis of the Neurolepticum Olanzapine (Zyprexa)

10 May 2024 | Contributor(s): Hartwig, Jan, Ceylan, Sascha, Kupracz, Lukas, Coutable, Ludovic, Kirschning, Andreas

Hot chemistry! High-frequency inductive heating and flow chemistry are an ideal match for high-temperature synthesis. This is demonstrated in the multistep flow synthesis of the neurolepticum olanzapine (Zyprexa) that included three reactions with inductive heating and two purification steps...

Heterogeneous Crystallization as a Process Intensification Technology in an Integrated Continuous Manufacturing Process for Pharmaceuticals

09 Jun 2023 | Contributor(s): Testa, CJ, Shvedova, KHu, CT, Wu, W, Born, SC, Takizawa, B, Mascia, S

Continuous heterogeneous crystallization processes in mixed-suspension mixed-product removal (MSMPR) crystallizers of different configurations (e.g., single-stage cooling, multistage cooling, and multistage evaporative cooling) are developed, in which an active pharmaceutical ingredient...

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

09 Jun 2023 | Contributor(s): Yu, E, Mangunuru, HPRTelang, NS, Kong, CJ, Verghese, J, Gilliland, SE, Ahmad, S, Dominey, RN, Gupton, BF

Numerous synthetic methods for the continuous preparation of fine chemicals and active pharmaceutical ingredients (API's) have been reported in recent years resulting in a dramatic improvement in process efficiencies. Herein we report a highly efficient continuous synthesis of the antimalarial...

Highly Efficient Synthesis of HIV NNRTI Doravirine

25 Jun 2024 | Contributor(s): Gauthier, Donald R., Sherry, Benjamin D., Cao, Yang, Journet, Michel, Humphrey, Guy, Itoh, Tetsuji, Tschaen, David M.

The development of an efficient and robust process for the production of HIV NNRTI doravirine is described. The synthesis features a continuous aldol reaction as part of a de novo synthesis of the key pyridone fragment. Conditions for the continuous flow aldol reaction were derived using...

Highly Selective, Kinetically Driven Polymorphic Selection in Microfluidic Emulsion-Based Crystallization and Formulation

09 Jun 2023 | Contributor(s): Leon, RAL, Badruddoza, AMZheng, L, Yeap, EWQ, Toldy, AI, Wong, KY, Hatton, TA, Khan, SA

We present a simple, potentially generalizable method to create highly monodisperse spherical microparticles (SMs) of similar to 200 mu m size containing active pharmaceutical ingredient (API) crystals and a macromolecular excipient, with unprecedented, highly specific, and selective control over...

Holistic Control Strategies for Continuous Manufacturing

09 Jun 2023 | Contributor(s): Moore, Christine, Garcia, Thomas, Hausner, Douglas B., Ben-Anat, Inna

Innovative technologies such as continuous manufacturing (CM) bring speed, efficiency, and agility to pharmaceutical manufacturing together with enhanced process robustness and assurance of product quality. During CM, material is simultaneously charged and discharged into process unit operations....

Hot melt extrusion technology for continuous manufacturing

09 Jun 2023 | Contributor(s): Furqan Tahir, Lovett. David

Hot melt extrusion (HME), a manufacturing technique traditionally used in the plastic and food industries, is now attracting significant interest from the pharmaceutical manufacturing sector. This is primarily because HME enables the continuous manufacture of a wide variety of dosage...

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation

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

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently...

How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems

09 Jun 2023 | Contributor(s): Sarang Oka, Muzzio, Fernando

How to Design and Implement Powder-to-Tablet Continuous Manufacturing Systems provides a comprehensive overview on the considerations necessary for the design of continuous pharmaceutical manufacturing processes. The book covers both the theory and design of continuous processing of associated...

How to measure coating thickness of tablets: Method comparison of optical coherence tomography, near-infrared spectroscopy and weight-, height- and diameter gain

09 Jun 2023 | Contributor(s): Wahl, P. R., Peter, A., Wolfgang, M., Khinast, J. G.

Film coating of pharmaceutical dosage forms, such as tablets and pellets, can be used to tailor the drug release profile. With that regard, a uniform coating thickness of a single tablet (intra-tablet), all tablets (inter-tablet) and subsequent batches (inter-batch) is crucial. We present a...

Hybrid advanced control of flexible multipurpose continuous tablet manufacturing process via direct compaction

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

With numerous case studies throughout, this valuable guide is ideal for those engaged in, or learning about, continuous processing in pharmaceutical manufacturing.

Hypromellose - A traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery

09 Jun 2023 | Contributor(s): Maskova, Eliska, Kubova, Katerina, Raimi-Abraham, Bahijja T., Vllasaliu, Driton, Vohlidalova, Eva, Turanek, Jaroslav, Masek, Josef

Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix systems. The choice of numerous viscosity grades and molecular weights available from different manufacturers provides a great...

ICAS-PAT: A software for design, analysis and validation of PAT systems

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

In chemicals based product manufacturing, as in pharmaceutical, food and agrochemical industries, efficient and consistent process monitoring and analysis systems (PAT systems) have a very important role. These PAT systems ensure that the chemicals based product is manufactured with the specified...

Identifying a Loss-in-Weight Feeder Design Space Based on Performance and Material Properties

09 Jun 2023 | Contributor(s): Li, Tianyi, Scicolone, James V. Sanchez, Eric, Muzzio, Fernando J.

Powder properties, such as density and adhesion, can cause large variability in the flow rate of ingredients fed from feeders, which can propagate through the system. Knowing an ideal range of operation and correlating powder properties to process performance can result in faster optimization of...

Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

09 Jun 2023 | Contributor(s): Vandevivere, Lise, Vangampelaere, Maxine, Portier, Christoph, de Backere, Cedrine, Hausler, Olaf, De Beer, Thomas, Vervaet, Chris, Vanhoorne, Valerie

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable...

Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation

09 Jun 2023 | Contributor(s): Willecke, N., Szepes, A., Wunderlich, M., Remon, J. P., Vervaet, C., De Beer, T.

The overall objective of this work is to understand how excipient characteristics influence the process and product performance for a continuous twin-screw wet granulation process. The knowledge gained through this study is intended to be used for a Quality by Design (QbD)-based formulation...

Impact of blend properties and process variables on the blending performance

09 Jun 2023 | Contributor(s): Bekaert, B, Grymonpre, W, Novikova, A, Vervaet, C, Vanhoorne, V

In this study, quantitative relationships were established between blend properties, process settings and blending responses via multivariate data-analysis. Four divergent binary blends were composed in three different ratios and processed at various throughputs and impeller speeds. Additionally,...

Impact of blend properties on die filling during tableting

09 Jun 2023 | Contributor(s): Van Snick, B., Grymonpre, W., Dhondt, J., Pandelaere, K., Di Pretoro, G., Remon, J. P., De Beer, T., Vervaet, C., Vanhoorne, V.

Based on characterization of a wide range of fillers and APIs, thirty divergent blends were composed and subsequently compressed on a rotary tablet press, varying paddle speed and turret speed. The tablet weight variability was determined of 20 grab samples consisting of each 20 tablets....

Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients

09 Jun 2023 | Contributor(s): De;Souza, JM, Galaverna, RDe, Souza, AAN, Brocksom, TJ, Pastre, JC, De, Souza, ROMA, De;Oliveira, KT

We present a comprehensive review of the advent and impact of continuous flow chemistry with regard to the synthesis of natural products and drugs, important pharmaceutical products and definitely responsible for a revolution in modem healthcare. We detail the beginnings of modern drugs and the...

Impact of Critical Material Attributes (CMAs)-Particle Shape on Miniature Pharmaceutical Unit Operations

09 Jun 2023 | Contributor(s): Azad, Mohammad A., Capellades, Gerard Wang, Allison B. Klee, David M., Hammersmith, Gregory, Rapp, Kersten, Brancazio, David, Myerson, Allan S.

The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA)...

Impact of excipients on batch and continuous powder blending

09 Jun 2023 | Contributor(s): Jaspers, M, de, Wit, MTWKulkarni, SS, Meir, B, Janssen, PHM, van, Haandel, MMW, Dickhoff, BHJ

Stimulated by Pharma 4.0, the pharmaceutical industry is changing from batch-wise to continuous manufacturing. Therefore, individual processing steps such as blending of the active pharmaceutical ingredient (API) with excipients have to be re-designed to continuous operations. In this study,...