Real-time monitoring of the moisture content of filter cakes in vacuum filters by a novel soft sensor

09 Jun 2023 | Contributor(s): Huttunen, Manu, Nygren, Lauri Kinnarinen, Teemu Ekberg, Bjarne, Lindh, Tuomo, Karvonen, Vesa, Ahola, Jero, Häkkinen, Antti

The moisture content of filter cakes is probably the most important characteristic that should be kept at a desired level in industrial cake filtration applications to maintain consistent product quality and minimize energy consumption. Most of the currently applied methods for contactless...

Recent Advances in Co-processed APIs and Proposals for Enabling Commercialization of These Transformative Technologies

09 Jun 2023 | Contributor(s): Schenck, L, Erdemir, DGorka, LS, Merritt, JM, Marziano, I, Ho, R, Lee, M, Bullard, J, Boukerche, M, Ferguson, S, Florence, AJ, Khan, SA, Sun, CC

Optimized physical properties (e.g., bulk, surface/interfacial, and mechanical properties) of active pharmaceutical ingredients (APIs) are key to the successful integration of drug substance and drug product manufacturing, robust drug product manufacturing operations, and ultimately to attaining...

Raman Spectroscopy

09 Jun 2023

Standard highlights the use of Raman spectroscopy to ensure successful application for measuring pharmaceutical products.

Quantitative Solution Measurement for the Selection of Complexing Agents to Enable Purification by Impurity Complexation

09 Jun 2023 | Contributor(s): Weber, CC, Wood, GPFKunov-Kruse, AJ, Nmagu, DE, Trout, BL, Myerson, AS

The removal of carboxylic acid impurities from amide targets has been accomplished through crystallization featuring a complexing agent in solution. The interaction between the complexing agents and impurities was examined using isothermal titration calorimetry and the free energy of association...

Raman Spectroscopy for Monitoring the Continuous Crystallization of Carbamazepine

09 Jun 2023 | Contributor(s): Acevedo, D, Mohammad, Adil, Pavurala, Naresh, Wu, Wei-Lee, O'Connor, Thomas F., Nagy, Zoltan K, Yang, Xiaochuan, Cruz, CN

Crystallization has a significant impact on the properties of the active pharmaceutical ingredient (API) since it is the final step in the manufacturing of the drug substance and determines particle size distribution, purity, shape, and polymorphs. Many publications have focused on the...

Rapid and nondestructive analysis of pharmaceutical products using near-infrared diffuse reflectance spectroscopy

09 Jun 2023 | Contributor(s): Li, P, Du, GRCai, WS, Shao, XG

Near-infrared diffuse reflectance spectroscopy (NIRDRS) was applied to classification and quantification of azithromycin tablets with the aid of chemometric multivariate analysis. Repeatability was investigated by repeated measurements, and the effect of morphology was examined by preparing the...

Rapid On-Demand Synthesis of Lomustine under Continuous Flow Conditions

09 Jun 2023 | Contributor(s): Jaman, Z, Sobreira, TJPMufti, A, Ferreira, CR, Cooks, RG, Thompson, DH

Lomustine, an important agent for treatment of brain tumors and Hodgkin's lymphoma, has been synthesized using continuous flow methodology. Desorption electrospray ionization mass spectrometry (DESI-MS) was used to quickly explore a large number of reaction conditions for one of the reaction...

Real time monitoring of powder blend bulk density for coupled feed-forward/feed-back control of a continuous direct compaction tablet manufacturing process

09 Jun 2023 | Contributor(s): Singh, Ravendra, Román-Ospino, Andrés D. Romañach, Rodolfo J. Ierapetritou, Marianthi, Ramachandran, Rohit

The pharmaceutical industry is strictly regulated, where precise and accurate control of the end product quality is necessary to ensure the effectiveness of the drug products. For such control, the process and raw materials variability ideally need to be fed-forward in real time into an automatic...

Raw material variability of an active pharmaceutical ingredient and its relevance for processability in secondary continuous pharmaceutical manufacturing

09 Jun 2023 | Contributor(s): Stauffer, F, Vanhoorne, VPilcer, G, Chavez, PF, Rome, S, Schubert, MA, Aerts, L, De;Beer, T

Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product...

Real-time assessment of critical quality attributes of a continuous granulation process

09 Jun 2023 | Contributor(s): Fonteyne, Margot, Vercruysse, Jurgen, Díaz, Damián Córdoba, Gildemyn, Delphine, Vervaet, Chris, Remon, Jean Paul, De Beer, Thomas

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories,...

Quality Risk Management

09 Jun 2023

Guideline establishes the environment surrounding risk detection and mitigation in order to maintain high quality pharmaceutical products.

Process scheduling under uncertainty : Review and challenges

09 Jun 2023 | Contributor(s): Li, Zukui, Ierapetritou, Marianthi

Uncertainty is a very important concern in production scheduling since it can cause infeasibilities and production disturbances. Thus scheduling under uncertainty has received a lot of attention in the open literature in recent years from chemical engineering and operations research communities....

Process Simulation and Control for Continuous Pharmaceutical Manufacturing of Solid Drug Products

09 Jun 2023 | Contributor(s): Ierapetritou, Marianthi, Escotet-Espinoza, M Sebastian, Singh, Ravendra

This chapter focuses on the application and development of unit operation and process models of the major routes of continuous solid dose manufacturing. Process models developed in the chapter are very important tools for the design of control system. The chapter also focuses on the current...

Progress of Pharmaceutical Continuous Crystallization

09 Jun 2023 | Contributor(s): Zhang, DJ, Xu, SJDu, SC, Wang, JK, Gong, JB

Crystallization is an important unit operation in the pharmaceutical industry. At present, most pharmaceutical crystallization processes are performed in batches. However, due to product variability from batch to batch and to the low productivity of batch crystallization, continuous...

Process optimization for continuous extrusion wet granulation

09 Jun 2023 | Contributor(s): Tan, L, Carella, AJ, Ren, YK, Lo, JB

Three granulating binders in high drug-load acetaminophen blends were evaluated using high shear granulation and extrusion granulation. A polymethacrylate binder enhanced tablet tensile strength with rapid disintegration in simulated gastric fluid, whereas polyvinylpyrrolidone and hydroxypropyl...

Process scheduling under uncertainty : Review and challenges

09 Jun 2023 | Contributor(s): Li, Zukui, Ierapetritou, Marianthi

Uncertainty is a very important concern in production scheduling since it can cause infeasibilities and production disturbances. Thus scheduling under uncertainty has received a lot of attention in the open literature in recent years from chemical engineering and operations research communities....

Process Simulation and Control for Continuous Pharmaceutical Manufacturing of Solid Drug Products

09 Jun 2023 | Contributor(s): Ierapetritou, Marianthi, Escotet-Espinoza, M Sebastian, Singh, Ravendra

This chapter focuses on the application and development of unit operation and process models of the major routes of continuous solid dose manufacturing. Process models developed in the chapter are very important tools for the design of control system. The chapter also focuses on the current...

Provoking an end-to-end continuous direct compression line with raw materials prone to segregation

09 Jun 2023 | Contributor(s): Lakio, Satu, Ervasti, Tuomas, Tajarobi, Pirjo, Wikstrom, Hakan, Fransson, Magnus, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Folestad, Staffan, Abrahmsen-Alami, Susanna, Korhonen, Ossi

Continuous manufacturing of solid oral dosage forms is promising for increasing the efficiency and quality of pharmaceutical production and products. In this study a whole train continuous direct compression (CDC) line has been provoked using challenging formulations typically prone to...

Quality Risk Assessment and Mitigation of Pharmaceutical Continuous Manufacturing Using Flowsheet Modeling Approach

09 Jun 2023 | Contributor(s): Tian, Geng;, Koolivand, Abdollah, Arden, Nilou S., Lee, Sau, O'Connor, Thomas F.

Integrated flowsheet modeling is an engineering approach that can provide a framework for understanding the impact of process dynamics on drug quality and associated risks during production, thereby facilitating the development of robust continuous processes. In this investigation, flowsheet...

Quantification of Inkjet-Printed Pharmaceuticals on Porous Substrates Using Raman Spectroscopy and Near-Infrared Spectroscopy

09 Jun 2023 | Contributor(s): Edinger, M, Iftimi, LDMarkl, D, Al-Sharabi, M, Bar-Shalom, D, Rantanen, J, Genina, N

The use of inkjet printing for pharmaceutical manufacturing is gaining interest for production of personalized dosage forms tailored to specific patients. As part of the manufacturing, it is imperative to ensure that the correct dose is printed. The aim of this study was to use inkjet printing...

Qualitative Assessment of a Multi-Scale, Compartmental PBM-DEM Model of a Continuous Twin-Screw Wet Granulation Process

09 Jun 2023 | Contributor(s): Barrasso, Dana, Ramachandran, Rohit

Wet granulation processes play a crucial role in solid oral dosage manufacturing processes. However, they are often designed empirically with poor efficiency. To implement quality-by-design, a more scientific understanding is desired to predict the effects of process and equipment design and...

Quality-by-Design III: Application of Near-Infrared Spectroscopy to Monitor Roller Compaction In-process and Product Quality Attributes of Immediate Release Tablets

09 Jun 2023 | Contributor(s): Kona, Ravikanth, Fahmy, Raafat M., Claycamp, Gregg, Polli, James E., Martinez, Marilyn, Hoag, Stephen W.

The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller...

Process dynamics and control of API manufacturing and purification processes

09 Jun 2023 | Contributor(s): Sen, Maitraye, Singh, Ravendra, Ramachandran, Rohit

The pharmaceutical industries have started transitioning toward continuous mode of manufacturing recently. Due to many advantages of the continuous manufacturing over the traditional alternatives, the industries are putting huge effort to efficiently adapt the continuous processing mode. However,...

Process Model for Enhancing Yield in Sterile Drug Product Manufacturing

09 Jun 2023 | Contributor(s): Yabuta, K, Hirao, M, Sugiyama, H

We present a process model for enhancing the yield in the manufacturing of sterile drug products, such as injectables, eye drops, or intravenous bags. The process typically consists of compounding, filtration, filling, and visual inspection and involves raw materials of active pharmaceutical...

Process Modeling and Simulation of Tableting-An Agent-Based Simulation Methodology for Direct Compression

09 Jun 2023 | Contributor(s): Martin, NL, Schomberg, AKFinke, JH, Abraham, TGM, Kwade, A, Herrmann, C

In pharmaceutical manufacturing, the utmost aim is reliably producing high quality products. Simulation approaches allow virtual experiments of processes in the planning phase and the implementation of digital twins in operation. The industrial processing of active pharmaceutical ingredients...