Exploratory studies in heat-assisted continuous twin-screw dry granulation: A novel alternative technique to conventional dry granulation

09 Jun 2023 | Contributor(s): Kallakunta, Venkata Raman, Patil, Hemlata, Tiwari, Roshan, Ye, Xingyou, Upadhye, Sampada, Vladyka, Ronald S., Sarabu, Sandeep, Kim, Dong Wuk, Bandari, Suresh, Repka, Michael A.

Dry granulation is the preferred technique for solvent-sensitive products, especially drugs with stability problems such as hydrolysis. Twin-screw granulation is a continuous granulation technique, offering a potential alternative to conventional dry granulation techniques such as roller...

Experimental determination of residence time distribution in continuous dry granulation

09 Jun 2023 | Contributor(s): Mangal, Haress, Kleinebudde, Peter

With increasing importance of continuous manufacturing, the interest in integrating dry granulation into a continuous manufacturing line is growing. Residence time distribution measurements are of importance as they provide information about duration of materials within the process. These data...

Evaluation of a Combined MHE-NMPC Approach to Handle Plant-Model Mismatch in a Rotary Tablet Press

09 Jun 2023 | Contributor(s): Huang, Yan-Shu, Reklaitis, Gintaras V.

The transition from batch to continuous processes in the pharmaceutical industry has been driven by the potential improvement in process controllability, product quality homogeneity, and reduction of material inventory. A quality-by-control (QbC) approach has been implemented in a variety of...

Estimation of Mass-Based Composition in Powder Mixtures Using Extended Iterative Optimization Technology (EIOT)

09 Jun 2023 | Contributor(s): Shi, Zhenqi, Hermiller, James, García Muñoz, Salvador

The Extended Iterative Optimization Technology (EIOT) method is proposed as an extension to Muteki’s [I&ECR 2013;52 (35):12258–12268] Iterative Optimization Technology to address deviations from Beer–Lambert’s law in powders. The new method estimates the apparent spectrum for the pure species,...

Evaluation of crystallization kinetics of adipic acid in an oscillatory baffled crystallizer

09 Jun 2023 | Contributor(s): Brown, C. J., Ni, X.

For solution crystallization, nucleation can be characterized by the maximum sub-cooling (or metastable limit), which is known to vary with numerous process parameters. The relationship between the metastable limit and cooling rate is of particular interest, as it can be utilized to derive...

Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous Green Granulation Process and Design-of-Experiment Approach

09 Jun 2023 | Contributor(s): Almutairy, Bjad K., Khafagy, El-Sayed, Alalaiwe, Ahmed, Aldawsari, Mohammed F., Alshahrani, Saad M., Alsulays, Bader B., Alshetaili, Abdullah S., Alshehri, Sultan M, Fayed, Mohamed H.

Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this Research Article, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting...

Ensuring tablet quality via model-based control of a continuous direct compaction process

09 Jun 2023 | Contributor(s): Kirchengast, M, Celikovic, SRehrl, J, Sacher, S, Kruisz, J, Khinast, J, Horn, M

Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders,...

Evaluating the potential for optimization of axial back-mixing in continuous pharmaceutical manufacturing

09 Jun 2023 | Contributor(s): Peterwitz, M, Schembecker, G

In continuous pharmaceutical manufacturing, the degree of back-mixing has two contrary effects on the propagation of disturbances through a process. Firstly, back-mixing results in the contamination of adjacent material by strong disturbances and additional losses. However, the available...

Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Vargas, Jenny, Roman-Ospino, Andres, Sanchez, Eric, Romañach, Rodolfo

Purpos: A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis....

End-to-End Continuous Manufacturing of Pharmaceuticals: Integrated Synthesis, Purification, and Final Dosage Formation

09 Jun 2023 | Contributor(s): Mascia, Salvatore, Heider, Patrick L., Zhang, Haitao, Lakerveld, Richard, Benyahia, Brahim, Barton, Paul I., Braatz, Richard D., Cooney, Charles L., Evans, James M. B., Jamison, Timothy F., Jensen, Klavs F., Myerson, Allan S., Trout, Bernhardt L.

A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug...

Evaluation of an in-line NIR spectroscopic method for the determination of the residence time in a tablet press

09 Jun 2023 | Contributor(s): De Leersnyder, Fien, Vanhoorne, Valérie, Kumar, Ashish, Vervaet, Chris, De Beer, Thomas

In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on...

End-to-End Continuous Manufacturing of Pharmaceuticals: Integrated Synthesis, Purification, and Final Dosage Formation

09 Jun 2023 | Contributor(s): Mascia, Salvatore, Heider, Patrick L., Zhang, Haitao, Lakerveld, Richard, Benyahia, Brahim, Barton, Paul I., Braatz, Richard D., Cooney, Charles L., Evans, James M. B., Jamison, Timothy F., Jensen, Klavs F., Myerson, Allan S., Trout, Bernhardt L.

A series of tubes: The continuous manufacture of a finished drug product starting from chemical intermediates is reported. The continuous pilot-scale plant used a novel route that incorporated many advantages of continuous-flow processes to produce active pharmaceutical ingredients and the drug...

Ensuring tablet quality via model-based control of a continuous direct compaction process

09 Jun 2023 | Contributor(s): Kirchengast, M, Celikovic, SRehrl, J, Sacher, S, Kruisz, J, Khinast, J, Horn, M

Switching from batch to continuous pharmaceutical production offers several advantages, such as an increased productivity, a steady product quality, and decreased costs. This paper presents a control strategy for direct compaction on a continuous tablet production line consisting of two feeders,...

Estimation of Mass-Based Composition in Powder Mixtures Using Extended Iterative Optimization Technology (EIOT)

09 Jun 2023 | Contributor(s): Shi, Zhenqi, Hermiller, James, García Muñoz, Salvador

The Extended Iterative Optimization Technology (EIOT) method is proposed as an extension to Muteki’s [I&ECR 2013;52 (35):12258–12268] Iterative Optimization Technology to address deviations from Beer–Lambert’s law in powders. The new method estimates the apparent spectrum for the pure species,...

Evaluation of an in-line NIR spectroscopic method for the determination of the residence time in a tablet press

09 Jun 2023 | Contributor(s): De Leersnyder, Fien, Vanhoorne, Valérie, Kumar, Ashish, Vervaet, Chris, De Beer, Thomas

In the current study, the ability to use in-line NIR inside the feed frame of a tablet press to monitor the residence time distribution inside the tablet press was investigated. Pulse-response experiments were performed. In-line measurements inside the feed frame were compared to measurements on...

Evaluation of Analytical and Sampling Errors in the Prediction of the Active Pharmaceutical Ingredient Concentration in Blends From a Continuous Manufacturing Process

09 Jun 2023 | Contributor(s): Vargas, Jenny, Roman-Ospino, Andres, Sanchez, Eric, Romañach, Rodolfo

Purpos: A near-infrared (NIR) spectroscopic method was developed for real time analysis of the active pharmaceutical ingredient (API) in blends from a continuous manufacturing process. The sampling and analytical errors of these determinations were estimated through variographic analysis....

Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC)

09 Jun 2023 | Contributor(s): Pawar, Pallavi, Wang, Yifan, Keyvan, Golshid, Callegari, Gerardo, Cuitino, Alberto, Muzzio, Fernando

A method for predicting dissolution profiles of directly compressed tablets for a fixed sustained release formulation manufactured in a continuous direct compaction (CDC) system is presented. The methodology enables real-time release testing (RTRt). Tablets were made at a target drug...

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

09 Jun 2023 | Contributor(s): Brown, CJ, McGlone, TYerdelen, S, Srirambhatla, V, Mabbott, F, Gurung, R, Briuglia, ML, Ahmed, B, Polyzois, H, McGinty, J, Perciballi, F, Fysikopoulos, D, MacFhionnghaile, P, Siddique, H, Raval, V, Harrington, TS, Vassileiou, AD, Robertson, M, Prasad, E, Johnston, A, Johnston, B, Nordon, A, Srai, JS, Halbert, G, ter, Horst, JH, Price, CJ, Rielly, CD, Sefcik, J, Florence, AJ

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of...

Effects of powder flow properties and shear environment on the performance of continuous mixing of pharmaceutical powders

09 Jun 2023 | Contributor(s): Vanarase, AU, Osorio, JG, Muzzio, FJ

This paper focuses on two aspects of continuous powder mixing, namely characterizing the effects of material properties on the bulk powder flow behavior, and developing continuous blending strategies suitable for cohesive materials. The relative effects of process parameters and material...

Effects of process parameters on tablet critical quality attributes in continuous direct compression: a case study of integrating data-driven statistical models and mechanistic compaction models

09 Jun 2023 | Contributor(s): Huang, Zhuangrong, Galbraith, Shaun C., Cha, Bumjoon, Liu, Huolong, Park, Seoyoung, Flamm, Matthew H., Metzger, Matt, Tantuccio, Anthony, Yoon, Seongkyu

Continuous manufacturing of oral-dosage drug products is increasing the need for rigorous process understanding both from a process design and control perspective. The purpose of this study is to develop a methodology that analyzes the effects of upstream process parameters on continuous tablet...

Effects of processing parameters and blade patterns on continuous pharmaceutical powder mixing

09 Jun 2023 | Contributor(s): Osorio, JG, Muzzio, FJ

The present study summarizes the experimental characterization of a new continuous powder mixer (GCG-70 by Glatt (R)) using common pharmaceutical ingredients. The powder hold-up and residence time distribution were used to characterize the bulk behavior of the mixer as a function of impeller...

Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC)

09 Jun 2023 | Contributor(s): Pawar, Pallavi, Wang, Yifan, Keyvan, Golshid, Callegari, Gerardo, Cuitino, Alberto, Muzzio, Fernando

A method for predicting dissolution profiles of directly compressed tablets for a fixed sustained release formulation manufactured in a continuous direct compaction (CDC) system is presented. The methodology enables real-time release testing (RTRt). Tablets were made at a target drug...

Effects of Process and Design Parameters on Granule Size Distribution in a Continuous High Shear Granulation Process

09 Jun 2023 | Contributor(s): Meng, Wei, Oka, Sarang, Liu, Xue, Omer, Thamer, Ramachandran, Rohit, Muzzio, Fernando J.

Wet granulation is widely used in the pharmaceutical industry. This advantageous technology is capable of enhancing compression and powder handling, decreasing ingredient segregation, and promoting blend and content uniformity. Currently, a high level of interest exists in the continuous version...

Effects of rotation rate, mixing angle, and cohesion in two continuous powder mixers-A statistical approach

09 Jun 2023 | Contributor(s): Portillo, PM, Ierapetritou, MG, Muzzio, FJ

In this paper we examine the effect of rotation rate, mixing angle, and cohesion on the powder residence time and the content uniformity of the blend exiting from two continuous powder mixers. In addition, differences in mixing performance between the two blenders are examined. Analysis of...

Effects of Shear and Electrical Properties on Flow Characteristics of Pharmaceutical Blends

09 Jun 2023 | Contributor(s): Pingali, KC, Tomassone, MS, Muzzio, FJ

This article examines the effects and interactions of shear rate, shear strain on electrical and flow properties of pharmaceutical blends. An unexpectedly strong relation between the flow and passive electrical properties of powders is observed to depend on the shear history of the powder bed....