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,...

Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol

09 Jun 2023 | Contributor(s): Urwin, SJ, Yerdelen, SHouson, I, ter;Horst, JH

A thorough, systematic study into the effect that structurally related impurities have on both the process and product quality during the crystallization of an active pharmaceutical ingredient is presented. The presence of acetanilide and metacetamol influences the crystallization and product...

Impact of material properties and process variables on the residence time distribution in twin screw feeding equipment

09 Jun 2023 | Contributor(s): Van Snick, B, Kumar, A, Verstraeten, M, Pandelaere, K, Dhondt, J, Di Pretoro, G, De Beer, T, Vervaet, C, Vanhoorne, V

Screw feeders are integrated as dispensing units in most continuous manufacturing platforms. Hence, characterizing and modelling the residence time distribution (RTD) of materials in feeders is indispensable to understand the traceability of raw materials from the drum till tablet, enabling the...

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation

09 Jun 2023 | Contributor(s): Vercruysse, J, Burggraeve, A., Fonteyne, M., Cappuyns, P., Delaet, U., Van Assche, I., De Beer, T., Remon, J. P., Vervaet, C.

Twin screw granulation (TSG) has been reported by different Research Article groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution...

Impact of surface roughness of pre-treated punches and powder properties on prevention of sticking during pharmaceutical tableting

09 Jun 2023 | Contributor(s): Takeuchi, Y, Murase, YTahara, K, Takeuchi, H

In the present study, surface-modified punches with different roughness were evaluated for their ability to prevent sticking during pharmaceutical tableting using a single punch machine. The surface roughness of the punch faces was assessed using a laser microscope. Acetaminophen and ibuprofen...

Impact of Vertical Blender Unit Parameters on Subsequent Process Parameters and Tablet Properties in a Continuous Direct Compression Line

09 Jun 2023 | Contributor(s): Kreiser, MJ, Wabel, C, Wagner, KG

The continuous manufacturing of solid oral-dosage forms represents an emerging technology among the pharmaceutical industry, where several process steps are combined in one production line. As all mixture components, including the lubricant (magnesium stearate), are passing simultaneously through...

Implementation of an advanced hybrid MPC–PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plan

09 Jun 2023 | Contributor(s): Singh, Ravendra, Sahay, Abhishek, Karry, Krizia, Muzzio, Fernando, Ierapetritou, Marianthi, Ramachandran, Rohit

It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to...

Implementation of an online thermal imaging to study the effect of process parameters of roller compactor

09 Jun 2023 | Contributor(s): Omar, Chalak S., Hounslow, Michael J., Salman, Agba D.

During roller compaction, not only the properties of the primary powder affect the product quality but also the process parameters. Any change in the process parameters during roller compaction will result in changing the properties of the ribbon. In this study, the temperature of the ribbon...

Implementation of control system into continuous pharmaceutical manufacturing pilot plant (powder to tablet)

09 Jun 2023 | Contributor(s): Singh, Ravendra

Real-time process control is highly desired for efficient quality by design (QbD)-based pharmaceutical manufacturing. A control system ensures the predefined end-product quality, satisfies the high regulatory constraints, facilitates real-time release of the product, and optimizes the resources....

Implementation of Near-Infrared Spectroscopy for In-Line Monitoring of a Dehydration Reaction in a Tubular Laminar Reactor

09 Jun 2023 | Contributor(s): Mitic, A, Cervera-Padrell, AEMortensen, AR, Skovby, T, Dam-Johansen, K, Javakhishvili, I, Hvilsted, S, Gernaey, KV

Production of active pharmaceutical ingredients (APIs), fine chemicals, food products, and so on has in recent years been focused on implementing process intensification and process optimization tools. Lower costs and higher selectivity as well as better sustainability and competitiveness are the...

Implementing Continuous Manufacturing for the Final Methylation Step in the AMG 397 Process to Deliver Key Quality Attributes

09 Jun 2023 | Contributor(s): Tom, JK, Achmatowicz, MMBeaver, MG, Colyer, J, Ericson, A, Hwang, TL, Jiao, N, Langille, NF, Liu, M, Lovette, MA, Sangodkar, RP, Kumar, SS, Spada, S, Perera, D, Sheeran, J, Campbell, K, Doherty, T, Ford, DD, Fang, YQ, Rossi, E, Santoni, G, Cui, S, Walker, SD

In this article, we describe the process development efforts to improve the final methylation step in the AMG 397 drug substance process, culminating in the execution of a Good Manufacturing Practice (GMP) continuous manufacturing process. During the development, batch kinetic studies and...

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...

Granulation of increasingly hydrophobic formulations using a twin screw granulator

09 Jun 2023 | Contributor(s): Yu, Shen, Reynolds, Gavin K., Huang, Zhenyu, de Matas, Marcel, Salman, Agba D.

The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has...

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...