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...

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...

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...

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...

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...

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...

Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery

09 Jun 2023 | Contributor(s): Thompson, M. R., Weatherley, S., Pukadyil, R. N., Sheskey, P. J.

This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work...

Forbidden Chemistries - Paths to a Sustainable Future Engaging Continuous Processing

09 Jun 2023 | Contributor(s): Gutmann, B, Kappe, CO

Optimizing current chemical processes alone does not yield the improvements required in the fine chemical and pharmaceutical industries. At least partially, a switch from batch to continuous manufacturing is needed. Cost-, time-, and atom-efficient routes frequently demand the application of high...

Formation of Ciprofloxacin-Isonicotinic Acid Cocrystal Using Mechanochemical Synthesis Routes-An Investigation into Critical Process Parameters

09 Jun 2023 | Contributor(s): Karimi-Jafari, M, Ziaee, AO'Reilly, E, Croker, D, Walker, G

The mechanochemical synthesis of cocrystals has been introduced as a promising approach of formulating poorly water-soluble active pharmaceutical ingredients (APIs). In this study, hot-melt extrusion (HME) as a continuous process and grinding and ball milling as batch processes were employed to...

Formation of organic molecular nanocrystals under soft confinement

09 Jun 2023 | Contributor(s): Yang, XC, Ong, TCMichaelis, VK, Heng, S, Griffin, RG, Myerson, AS

Methods to produce nano-sized organic molecular crystals in thin films are of great interest in the pharmaceutical industry due to the potential benefit of increased solubility of poorly soluble drugs and the advantages of film-based dosage forms over traditional tablet/capsule-based dosage...

From circular synthesis to material manufacturing: advances, challenges, and future steps for using flow chemistry in novel application area

09 Jun 2023 | Contributor(s): Sivo, A, Galaverna, RDGomes, GR, Pastre, JC, Vile, G

Continuous-flow technologies are becoming increasingly relevant in the chemistry field. The vast arrays of reactor design, in terms of structural geometry, mixing, and residence time, the modularity of these systems, adaptable for every application, and the easy downstream integrations are at the...

From form to function: Crystallization of active pharmaceutical ingredients

09 Jun 2023 | Contributor(s): Variankaval, Narayan, Cote, Aaron S., Doherty, Michael F.

In this perspective, we describe the state-of-the-art in API crystal product and process design, highlight barriers that currently prevent the production of better, cheaper crystalline products, and give our best estimate of where the field is going and should go during the next decade.

From powder to tablets: Investigation of residence time distributions in a continuous manufacturing process train as basis for continuous process verification

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

The essence of Continuous Manufacturing (CM) resides in the fact that continuous process units are directly connected to each other forming a continuous process train. The thorough understanding of material flow in this train based on suitable sensors, including on-line process analytical...

Future Supply Chains Enabled by Continuous Processing - Opportunities and Challenges

09 Jun 2023 | Contributor(s): Jagjit Singh Srai, Markus Krumme, Mauricio Futran, Clive Badman, Craig Johnston

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily “continuous processing”-based supply chain. The current predominantly “large batch” and centralized manufacturing system designed for the “blockbuster” drug has driven a slow-paced,...

Generic Framework for Crystallization Processes Using the Population Balance Model and Its Applicability

09 Jun 2023 | Contributor(s): Shaikh, Latif J., Bari, Atul H. Ranade, Vivek V., Pandit, Aniruddha B.

A generic modeling framework for batch cooling crystallization processes has been developed to understand the crystallization process from operational and modeling point of view. The generic framework for crystallization process modeling incorporates the characteristic dimensions of crystals and...

Global Regulatory Landscape

09 Jun 2023 | Contributor(s): Matsuda, Y

Continuous manufacturing (CM) of pharmaceuticals is a rapidly growing approach in the production of active pharmaceutical ingredients and finished products. The European Medicines Agency, the US Food and Drug Administration, and the Pharmaceuticals and Medical Devices Agency have independently...

Good Manufacturing Practice Guide for Active Pharmacetuical Ingredients

09 Jun 2023

Guideline highlgihts important aspects of manufacturing API.

Granulation development in batch-to-batch and continuous processes from a quality by design perspective

09 Jun 2023 | Contributor(s): Ko, Seung Jin, Lee, Ju-Hyun, Kang, Chin-Yang, Park, Jun-Bom

The process of quality by design (QbD) is of great importance in drug development. This review describes the design of experiments (DoE) method, which is an important component of QbD. DoE is predominantly divided into a screening phase and an optimization phase. The screening phase uses...

Flexibility in Drug Product Development: A Perspective

09 Jun 2023 | Contributor(s): Kapoor, Yash, Ferguson, Heidi, Skomski, Daniel, Daublain, Pierre, Troup, Gregory, Dalton, Chad, Ramasamy, Manoharan, Templeton, Allen

The process of bringing a drug to market involves innumerable decisions to refine a concept into a final product. The final product goes through extensive research and development to meet the target product profile and to obtain a product that is manufacturable at scale. Historically, this...