Manipulation of ionic liquid anion-solute-antisolvent interactions for the purification of acetaminophen

09 Jun 2023 | Contributor(s): Weber, CC, Kunov-Kruse, AJRogers, RD, Myerson, AS

Hydrogen bond donating cosolvents have been shown to significantly reduce the solubility of acetaminophen (AAP) in ionic liquids containing the acetate anion. Reduced solubility arises from competition for solvation by the acetate anion and can be used for the design of advanced separation...

Manufacturing of Solid Drug

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...

Mapping key process parameters to the performance of a continuous dry powder blender in a continuous direct compression system

09 Jun 2023 | Contributor(s): Palmer, J, Reynolds, GK, Tahir, F, Yadav, IK, Meehan, E, Holman, J, Bajwa, G

This work aims to expand the typical raw material attributes that can successfully be processed on a continuous direct compression line with a particular focus on the continuous dry powder blender. Three grades of Acetaminophen were investigated as model active pharmaceutical ingredients and...

Mass spectrometric directed system for the continuous-flow synthesis and purification of diphenhydramine

09 Jun 2023 | Contributor(s): Loren, BP, Wleklinski, MKoswara, A, Yammine, K, Hu, YY, Nagy, ZK, Thompson, DH, Cooks, RG

A highly integrated approach to the development of a process for the continuous synthesis and purification of diphenhydramine is reported. Mass spectrometry (MS) is utilized throughout the system for on-line reaction monitoring, off-line yield quantitation, and as a reaction screening module that...

Material Properties and Compressibility Using Heckel and Kawakita Equation with Commonly Used Pharmaceutical Excipients

09 Jun 2023 | Contributor(s): Choi, Du-Hyung, Kim, Nam-Ah Chu, Kyung-Rok Jung, Youn-Jung, Yoon, Jeong-Hyun, Jeong, Seong-Hoon

This study investigated basic material properties and compressibility of commonly used pharmaceutical excipients. Five classes of excipients are selected including starch, lactose, calcium phosphate, microcrystalline cellulose (MCC), and povidone. The compressibility was evaluated using...

Material tracking in a continuous direct capsule-filling process via residence time distribution measurements

09 Jun 2023 | Contributor(s): Kruisz, Julia, Rehrl, Jakob, Faulhammer, Eva, Witschnigg, Andreas, Khinast, Johannes G.

Continuous production of pharmaceuticals requires traceability from the raw material to the final dosage form. With that regard, understanding the residence time distribution (RTD) of the whole process and its unit operations is crucial. This work describes a structured approach to characterizing...

Mathematical development and comparison of a hybrid PBM-DEM description of a continuous powder mixing process

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

This paper describes the development of a multidimensional population balance model (PBM) which can account for the dynamics of a continuous powder mixing/blending process. The PBM can incorporate the important design and process conditions and determine their effects on the various critical...

Mathematical modeling and digital design of an intensified filtration-washing-drying unit for pharmaceutical continuous manufacturing

09 Jun 2023 | Contributor(s): Destro, Francesco, Hur, Inyoung Wang, Vivian Abdi, Mesfin, Feng, Xin, Wood, Erin, Coleman, Simon, Firth, Paul, Barton, Alastair, Barolo, Massimiliano, Nagy, Zoltan K.

This paper introduces a comprehensive mathematical model of a novel integrated filter-dryer carousel system, designed for continuously filtering, washing and drying a slurry stream into a crystals cake. The simulator includes models for dead-end filtration, cake washing and convective cake...

Mathematical modeling and experimental validation of continuous slug-flow tubular crystallization with ultrasonication-induced nucleation and spatially varying temperature

09 Jun 2023 | Contributor(s): Mozdzierz, Nicholas J., Lee, Yongkyu Hong, Moo Sun Benisch, Moritz H.P., Rasche, Michael L., Tropp, Uku Erik, Jiang, Mo, Myerson, Allan S., Braatz, Richard D.

Continuous slug-flow tubular crystallization has been explored by several Research Article groups in academia and industry as a way to produce crystals while having low capital equipment costs. In this crystallization type, slugs of slurry and gas consecutively travel through a tube, with a high...

Mathematical Modeling, Design, and Optimization of a Multisegment Multiaddition Plug-Flow Crystallizer for Antisolvent Crystallizations

09 Jun 2023 | Contributor(s): Su, Qinglin, Benyahia, Brahim Nagy, Zoltan K., Rielly, Chris D.

In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations....

Measurement of residence time distributions and material tracking on three continuous manufacturing lines

09 Jun 2023 | Contributor(s): Karttunen, Anssi-Pekka, Hörmannb,Theresa, De Leersnyder, Fien, Ketolainen, Jarkko, De Beer, Thomas, Hsiao, Wen-Kai, Korhonen, Ossi

Over the recent decade, benefits of continuous manufacturing (CM) of pharmaceutical products have been acknowledged widely. In contrast to batch processes, the product is not physically separated into batches in CM, which creates a few challenges. Product release is done for batches that should...

Laser triangulation as a fast and reliable method for determining ribbon solid fraction; focus on accuracy, precision, and measurement time

09 Jun 2023 | Contributor(s): Lillotte, Tim D, Bebernik, Paul, Keck, Johanna, Bommer, Moritz, Schroeder, Daniela, Wagner, Karl G.

Roller compaction and dry granulation represent well-established unit operations in the pharmaceutical industry. The ribbon solid fraction is classified as a critical quality attribute, that directly impacts final product quality and performance. The development and evaluation of novel methods...

Latent Variables-Based Process Modeling of a Continuous Hydrogenation Reaction in API Synthesis of Small Molecules

09 Jun 2023 | Contributor(s): Shi, Zhenqi, Zaborenko, Nikolay, Reed, David

Continuous manufacturing can be benefited by the use of the Quality by Design (QbD) strategy for robust process development and by the use of Process Analytical Technology (PAT) for real-time process monitoring and control. A successful implementation of QbD and PAT for continuous processes...

Life cycle analysis of solvent reduction in pharmaceutical synthesis using continuous adsorption for palladium removal

09 Jun 2023 | Contributor(s): Slater, CS, Savelski, MJ, Ruiz-Felix, MN

The life cycle emissions associated with the reduction of wastes from an adsorption process to remove palladium complexes in drug manufacture have been evaluated. The study assessed a green improvement to a process step in an active pharmaceutical ingredient synthesis where palladium catalyst is...

Light Diffraction Measurement of Particle Size

09 Jun 2023

Standard explain phenomena associated with light interaction with powder.

Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation

09 Jun 2023 | Contributor(s): Kumar, Ashish, Alakarjula, Maija, Vanhoorne, Valerie, Toiviainen, Maunu, De Leersnyder, Fien, Vercruysse, Jurgen, Juuti, Mikko, Ketolainen, Jarkko, Vervaet, Chris, Remon, Jean Paul, Gernaey, Krist V., De Beer, Thomas, Nopens, Ingmar

Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and...

Loss-in-Weight Feeding Trials Case Study: Pharmaceutical Formulation

09 Jun 2023 | Contributor(s): Engisch, WE, Muzzio, FJ

This article presents a case study of a continuous feeding strategy for five pharmaceutical components (active pharmaceutical ingredient (API), Prosolv HD90, crospovidone, magnesium stearate, and colloidal silicon dioxide), for the purpose of developing a direct compression continuous...

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

09 Jun 2023 | Contributor(s): Allenspach, Carl, Timmins, Peter, Lumay, Geoffroy, Holman, James, Minko, Tamara

Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both...

Low Energy Nanoemulsions as Templates for the Formulation of Hydrophobic Drugs

09 Jun 2023 | Contributor(s): Badruddoza, AM, Gupta, AMyerson, AS, Trout, BL, Doyle, PS

Most small molecule active pharmaceutical ingredients (APIs) are hydrophobic which poses formulation challenges due to their poor water solubility. Current approaches are energy intensive and involve presenting the API in a nanoparticle form that is then combined with other additives into a...

Lubricant based determination of design space for continuously manufactured high dose paracetamol tablets

09 Jun 2023 | Contributor(s): Taipale-Kovalainen, Krista, Karttunen, Anssi-Pekka, Ketolainen, Jarkko, Korhonen, Ossi

The objective of this study was to devise robust and stable continuous manufacturing process settings, by exploring the design space after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose paracetamol tablets. Experimental...

Lubrication empirical model to predict tensile strength of directly compressed powder blends

09 Jun 2023 | Contributor(s): Nassar, Joelle, Williams, Ben, Davies, Conrad, Lief, Kevin, Elkes, Richard

A new approach is proposed to support prediction of tablet tensile strength as a function of both solid fraction (and/or compression pressure) and extent of lubrication by using empirical data to parameterise the model. This is a pre-requisite for simulation of the compaction unit operation where...

Managing API raw material variability during continuous twin-screw wet granulation

09 Jun 2023 | Contributor(s): Stauffer, F, Vanhoorne, VPiker, G, Chavez, PF, Vervaet, C, De;Beer, T

Very few studies have investigated the impact of raw material variability upon the granule critical quality attributes (CQAs) produced via twin-screw wet granulation (i.e., granule size distribution, density, flowability). In this study, the impact of the raw material variability of an active...

Introduction to the Theory and Practice of Sampling

09 Jun 2023 | Contributor(s): Esbensen, Kim H

Sampling is an important, but sometimes hidden, part of everyday life in science, technology, industry, society and commerce where decisions are made based on analytical results, which must be based on reliable samples. However, there is a very long and complex pathway from heterogeneous...

Investigating the Effect of APAP Crystals on Tablet Behavior Manufactured by Direct Compression

09 Jun 2023 | Contributor(s): Ghazi, Nastaran, Liu, Zhanjie, Bhatt, Chinmay, Kiang, San, Cuitino, Alberto

In this work, the effect of API's (Active Pharmaceutical Ingredient) shape and size on tablet characteristics is investigated for high API dose formulation manufactured by direct compression. Three different classes of APAP (acetaminophen) are selected, and tablets are produced in both single and...

Investigation of Preprocessing and Validation Methodologies for PAT: Case study of the granulation and coating steps for the manufacturing of ethenzamide tablets

09 Jun 2023 | Contributor(s): Shibayama, Shojiro, Funatsu, Kimito

After the Food and Drug Association in the USA published guidelines on the enhanced use of process analytical technology (PAT) and continuous manufacturing, many studies regarding PAT and continuous manufacturing have been published. This paper describes a case study involving granulation and...