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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
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...
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Effects of processing parameters and blade patterns on continuous pharmaceutical powder mixing
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...
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Effects of rotation rate, mixing angle, and cohesion in two continuous powder mixers-A statistical approach
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...
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Effects of Shear and Electrical Properties on Flow Characteristics of Pharmaceutical Blends
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....
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Enabling real time release testing by NIR prediction of dissolution of tablets made by continuous direct compression (CDC)
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...
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Early detection of capping risk in pharmaceutical compacts
Contributor(s):: Xu, Xiaochi, Vallabh, Chaitanya Krishna Prasad, Hoag, Stephen W., Dave, Vivek S., Cetinkaya, Cetin
Capping is a common mechanical defect in tablet manufacturing, exhibited during or after the compression process. Predicting tablet capping in terms of process variables (e.g. compaction pressure and speed) and formulation properties is essential in pharmaceutical industry. In current work, a...
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Effect of force feeder on tablet strength during compression
Contributor(s):: Narang, Ajit S., Rao, Venkatramana M., Guo, Hang, Lu, Jian, Desai, Divyakant S.
Mechanical strength of tablets is an important quality attribute, which depends on both formulation and process. In this study, the effect of process variables during compression on tablet tensile strength and tabletability (the ratio of tensile strength to compression pressure) was investigated...
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Effect of formulation and process variables on lipid based sustained release tablets via continuous twin screw granulation: A comparative study
Contributor(s):: Kallakunta, Venkata Raman, Tiwari, Roshan, Sarabu, Sandeep, Bandari, Suresh, Repka, Michael A.
The current study's aim is to prepare lipid based sustained release tablets via a twin-screw granulation technique and compare those dosage forms with conventional techniques, namely wet granulation and direct compression. The granules were successfully manufactured in a single-step, continuous...
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Effect of High Shear Blending Protocols and Blender Parameters on the Degree of API Agglomeration in Solid Formulations
Contributor(s):: Llusa, M, Sturm, K, Sudah, O, Stamato, H, Goldfarb, DJ, Ramachandruni, H, Hammond, S, Smith, MR, Muzzio, FJ
This paper examines the effect of three protocols with several units and blender parameters on the mitigation of active pharmaceutical ingredient (API) agglomeration in solid formulations. The three protocols either preblend API with a portion of excipients in a high shear unit followed by...
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Effective Development of PAT Capability in Pharmaceutical Manufacturing
Contributor(s):: Hammond, Steve
Over the last ten years, the path to effective development of PAT has evolved, driven by the advent of continuous manufacturing. The development and deployment of PAT used for pharmaceutical manufacturing has arrived at a point where application development has been miniaturized and streamlined....
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Effects of Coating Materials and Processing Conditions on Flow Enhancement of Cohesive Acetaminophen Powders by High-Shear Processing With Pharmaceutical Lubricants
Contributor(s):: Wei, GG, Mangal, S, Denman, J, Gengenbach, T, Bonar, KL, Khan, RI, Qu, L, Li, TL, Zhou, Q
This study has investigated the surface coating efficiency and powder flow improvement of a model cohesive acetaminophen powder by high-shear processing with pharmaceutical lubricants through 2 common equipment, conical comil and high-shear mixer. Effects of coating materials and processing...
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Development of near infrared spectroscopic calibration models for in-line determination of low drug concentration, bulk density, and relative specific void volume within a feed frame
Contributor(s):: Ortega-Zuñiga, Carlos, Pinzón-De la Rosa, Carlos, Román-Ospino, Andrés D., Serrano-Vargas, Alberto, Romañach, Rodolfo J., Mendez, Rafael
This study describes the development of a near infrared (NIR) calibration model for real time determination of drug concentration, powder density, and porosity or relative specific void volume (RSVV) of 3.00%w/w acetaminophen blends within a feed frame. The NIR calibration model was developed...
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Development of Near Infrared Spectroscopy-based Process Monitoring Methodology for Pharmaceutical Continuous Manufacturing Using an Offline Calibration Approach
Contributor(s):: Hetrick, Evan, Barnes, Lukas E, Garrett, Aaron W, Rupard, Robert G, Kramer, Timothy T, Cooper, Tony M, Myers, David P, Shi, Zhenqi, Castle, Bryan C
A near-infrared (NIR) calibration was developed using an efficient offline approach to enable a quantitative partial least-squares (PLS) chemometric model to measure and monitor the concentration of active pharmaceutical ingredients (API) in powder blends in the feed frame (FF) of a tablet press....
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Diminished segregation in continuous powder mixing
Contributor(s):: Oka, S, Sahay, A, Meng, W, Muzzio, F
Binary powder mixtures with variable segregation tendencies were mixed in a tumbling batch blender and in a continuous convective tubular blender. The degree of homogeneity of the final blend obtained from the continuous blender was found to be much higher than that from the batch V-blender, for...
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Direct compaction properties of Zingiberis Rhizoma extracted powders coated with various shell materials: Improvements and mechanism analysis
Contributor(s):: Li, Zhe, Zhou, Miaomiao, Wu, Fei, Shen, Lan, Lin, Xiao, Feng, Yi
Direct compaction (DC) attracts more and more attention for tablet manufacturing; however, its application in natural plant product (NPP) tablets is still extremely limited. In this study, 8 kinds of composite particles (CPs) based on the Zingiberis Rhizoma extracted powder (ZR) (a natural plant...
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Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders
Contributor(s):: Grymonpre, W., Verstraete, G., Vanhoorne, V., Remon, J. P., De Beer, T., Vervaet, C.
The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all...
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Dry Powder Mixing Is Feasible in Continuous Twin Screw Extruder: Towards Lean Extrusion Process for Oral Solid Dosage Manufacturing
Contributor(s):: Mateo-Ortiz, Daniel, Villanueva-Lopez, Vladimir, Muddu, Shashank Venkat, Doddridge, Gregory D., Alhasson, Dana, Dennis, Michael C.
Using discrete element method (DEM) modeling and near-infrared (NIR) spectroscopy, the feasibility of powder mixing in the initial pre-melting zones of a twin screw extruder using two independent feeders was studied. Previous work in the pharmaceutical and food industry has focused on mixing when...
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Dual chamber cartridges in a continuous pharmaceutical freeze-drying concept: Determination of the optimal dynamic infrared heater temperature during primary drying
Contributor(s):: De Meyer, Laurens, Lammens, Joris, Vanbillemont, Brecht, Van Bockstal, Pieter Jan, Corver, Jos, Vervaet, Chris, Friess, Wolfgang, De Beer, Thomas
The applicability of DCCs in a continuous freeze-drying concept based on spin freezing and infrared heating was evaluated. Maximum applicable filling volume was evaluated. Secondly the mechanistic model for the determination of the optimal dynamic infrared heater temperature during primary drying...
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Development of an In-Line Near-Infrared Method for Blend Content Uniformity Assessment in a Tablet Feed Frame
Contributor(s):: Li, Yi, Anderson, Carl A, Drennen, James K, Airiau, Christian, Igne, Benoît
Process analytical technology (PAT) has shown great potential for in-line tableting process monitoring. The study focuses on the development and validation of an in-line near-infrared (NIR) spectroscopic method for the determination of content uniformity of blends in a tablet feed frame. An...
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Development of an in-line Raman spectroscopic method for continuous API quantification during twin-screw wet granulation
Contributor(s):: Harting Julia, Kleinebudde, Peter
Raman spectroscopy was evaluated as a process analytical technology (PAT) tool for continuous API quantification during twin-screw wet granulation. Therefore, a Raman probe was implemented in front of the granulator barrel. This setup enabled the collection of Raman spectra upon a constant...
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Development of directly compressible powders via co-spray drying
Contributor(s):: Gonnissen, Y., Remon, J. P., Vervaet, C.
Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility,...
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Development of drying-induced stresses in pharmaceutical granules prepared in continuous production line
Contributor(s):: Mezhericher, Maksim
The phenomenon of development of drying-induced stresses has been given a through consideration in the literature on drying of many products. At the same time, to the best of our knowledge, the open published sources contain no information on drying stresses in pharmaceutical granules prepared by...
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Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process
Contributor(s):: Puri, Vibha, Brancazio, Dave, Desai, Parind M., Jensen, Keith D., Chun, Jung-Hoon, Myerson, Allan S., Trout, Bernhardt L.
The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited Research Article on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore,...
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Development and Optimization of a Wet Granulation Process at Elevated Temperature for a Poorly Compactible Drug Using Twin Screw Extruder for Continuous Manufacturing
Contributor(s):: Meena, Anuprabha K, Desai, Divyakant, Serajuddin,, Abu T. M.
The objective of this study was to enhance tabletability of a poorly compactible drug, acetaminophen, by wet granulation using twin screw extruder at high temperature. It was desired that there would be minimum amounts of excipients used and the granules obtained after extrusion would be dry and...
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Development and Scale-Up of Diversion Strategy for Twin Screw Granulation in Continuous Manufacturing
Contributor(s):: Pawar, Pallavi, Clancy, Don, Gorringe, Lee, Barlow, Steve, Hesketh, Alex, Elkes, Richard
Successful implementation of Continuous Manufacturing technology requires real time product quality monitoring that can result into rejection strategies for material manufactured outside process control limits. In a twin screw granulation process, parameters like water content, powder feed rate,...