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Research Spending & Results

Award Detail

Awardee:RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
Doing Business As Name:Rutgers University New Brunswick
PD/PI:
  • Marianthi Ierapetritou
  • (908) 416-0019
  • mgi@udel.edu
Co-PD(s)/co-PI(s):
  • Rajesh N Dave
  • Fernando J Muzzio
  • James Litster
  • Eric H Erenrich
Award Date:11/25/2009
Estimated Total Award Amount: $ 1,800,000
Funds Obligated to Date: $ 1,800,000
  • FY 2010=$1,800,000
Start Date:12/01/2009
End Date:11/30/2013
Transaction Type:Grant
Agency:NSF
Awarding Agency Code:4900
Funding Agency Code:4900
CFDA Number:47.041
Primary Program Source:040100 NSF RESEARCH & RELATED ACTIVIT
Award Title or Description:Commercializing of Continuous Pharmaceutical Manufacturing Technology
Federal Award ID Number:0951845
DUNS ID:001912864
Parent DUNS ID:001912864
Program:EEC Innovation Awards

Awardee Location

Street:33 Knightsbridge Road
City:Piscataway
State:NJ
ZIP:08854-3925
County:Piscataway
Country:US
Awardee Cong. District:06

Primary Place of Performance

Organization Name:Rutgers University New Brunswick
Street:33 Knightsbridge Road
City:Piscataway
State:NJ
ZIP:08854-3925
County:Piscataway
Country:US
Cong. District:06

Abstract at Time of Award

This project will enable a vigorous commercialization effort for continuous pharmaceutical manufacturing technology developed by C-SOPS. This manufacturing approach can enable significant improvements in product quality, process robustness and productivity, and overall economic performance of the manufacturing process. A high level of interest exists at the present time in this technology, both by the US FDA, and by large pharmaceutical manufacturers, many of which are C-SOPS members. Many technology suppliers that are also members of C-SOPS have also indicated a keen interest in addressing this market need. The key missing element needed for successful commercialization is that, at the present time, no single technology supplier has all the necessary capabilities required to address this commercial opportunity. Thus, the main goal of this proposal is to assemble a coalition of technology suppliers, led by a systems integrator, and to enable them, by knowledge transfer and technical support, to commercialize fully integrated "turn key" manufacturing systems. The Intellectual Merit of this proposal has three main components. (1) This project will bring to the market place commercial-grade integrated technology for continuous manufacturing that is designed and optimized based on an in-depth understanding of the main components of the manufacturing system. (2) This project will expand the existing scope of continuous manufacturing at C-SOPS, which currently comprises uncoated tablets manufactured either via direct compression or dry granulation. We will add capabilities to enable the continuous manufacturing of both coated and uncoated tablets and capsules manufactured by direct blending, dry granulation, and wet granulation. (3) This project will demonstrate the impact of engineering methods for pharmaceutical product and process design and optimization, helping promote adoption of modern methodologies across an essential industry that at the present time uses empirical methods and batch processes as its main development and manufacturing paradigm. The Broader Impact of this project is also manifold: (1) Based on projected sales, we anticipate creation of 80 direct jobs, devoted to the commercialization, design, and implementation of continuous manufacturing systems, and perhaps twice as many indirect jobs by the end of the third year of this project. (2) The project will also create seven full time technical positions at center sites. (3) This project will demonstrate the capabilities of our ERC to develop innovative commercial-grade manufacturing technology, helping establish it as the premier worldwide center of academic research in pharmaceutical product and process design, setting the foundation for the long term viability and sustainability of our ERC. (4) Availability of commercial sources of integrated continuous technology will lead to its rapid adoption and implementation, and will lead to improved product quality, higher productivity rates, and lower cost of manufacturing, likely resulting in price reductions for the patient population.

Publications Produced as a Result of this Research

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A. S. El Hagrasy & P. Cruise & I. Jones & J. D. Litster "In-line Size Monitoring of a Twin Screw Granulation Process Using High-Speed Imaging" J. Pharm Innov, v., 2013, p..

Boukouvala, F., Muzzio, F. J. and Ierapetritou, M. G. "Predictive Modeling of Pharmaceutical Processes with Missing and Noisy Data" AIChE Journal, v.56, 2010, p.2860.

Deng, X., Davé, R. "Dynamic simulation of particle packing influenced by size, aspect ratio and surface energy" Granular Matter, v., 2013, p..

Matthew P. Mullarney, Lauren E. Beach, Rajesh N. Dave, Beth A. Langdon, Mark Polizzi and Daniel O. Blackwood "Applying dry powder coatings to pharmaceutical powders using a comil for improving powder flow and bulk density" Powder Technology, v.212, 2011, p.397.

Matthew P. Mullarney, Lauren E. Beach, Rajesh N. Dave, Beth A. Langdon, Mark Polizzi and Daniel O. Blackwood "Applying dry powder coatings to pharmaceutical powders using a comil for improving powder flow and bulk density" Powder Technology, v.212, 2011, p.397. doi:doi:10.1016/j.powtec.2011.06.008 

Deng, X., Scicolone, J.V., Davé, R.N. "Discrete element method simulation of cohesive particles mixing under magnetically assisted impaction" Powder Technology, v.243, 2013, p.96.

Ghoroi, C., Gurumurthy, L., McDaniel, D.J., Jallo, L.J., Davé, R.N. "Multi-faceted characterization of pharmaceutical powders to discern the influence of surface modification" Powder Technology, v.236, 2013, p.63.

Ghoroi, C., Han, X., To, D., Jallo, L., Gurumurthy, L., Davé, R.N. "Dispersion of fine and ultrafine powders through surface modification and rapid expansion" Chemical Engineering Science, v.85, 2013, p.11.

Han, X., Ghoroi, C., Dave, R., 2013 "Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading" Int J Pharm, v.442, 2013, p.74.

Han, X., Jallo, L., To, D., Ghoroi, C., Davé, R. "Passivation of high-surface-energy sites of milled ibuprofen crystals via dry coating for reduced cohesion and improved flowability" Journal of Pharmaceutical Sciences, v.102, 2013, p.2282.

Scicolone, J., Lepek, D., Louie, L., Davé, R. "Fluidization and mixing of nanoparticle agglomerates assisted via magnetic impaction" Journal of Nanoparticle Research, v.15, 2013, p.1.

Singh, R., Ierapetritou, M., Ramachandran, R. "System-wide hybrid model predictive control of a continuous pharmaceutical tablet manufacturing process via direct compaction" European Journal of Pharmaceutics and Biopharmaceutics, v., 2013, p..

Singh, R., Ierapetritou, M., Ramachandran, R "Hybrid advanced control of a flexible multipurpose continuous pharmaceutical tablet manufacturing process via direct compaction" Computer Aided Chemical Engineering, v.32, 2013, p.757.

Muzzio, F., Singh, R., Chaudhury, A., Rogers, A., Ramachandran, R. Ierapetritou, M. "Model- predictive design, control and optimization of pharmaceutical process" PharmTech magazine Europe, v.37, 2013, p.40.

Singh, R., Sahay, A., Oka, S., Liu, X., Ramachandran, R., Marianthi Ierapetritou, Fernando Muzzio, F. "Online monitoring, advanced control and operation of robust continuous pharmaceutical tablet manufacturing process" BioPharma magazine Asia, v.2, 2013, p..

Dubey, A., Sarkar, A., Ierapetritou, M., Wassgren, C., Muzzio, FJ "Computational Approaches for Studying the Granular Dynamics of Continuous Blending Processes, 1-DEM Based Methods" Macromolecular Materials and Engineering, v.296, 2011, p.290.

Boukouvala, F., Muzzio, F. J. and Ierapetritou, M. G. "Predictive Modeling of Pharmaceutical Processes with Missing and Noisy Data" AIChE Journal, v.56, 2010, p.2860. doi:10.1002/aic.12203 

F. Boukouvala, F. J. Muzzio, and Marianthi G. Ierapetritou "Dynamic Data-Driven Modeling of Pharmaceutical Processes" Industrial & Engineering Chemistry Research, v.50, 2011, p.6743.

R.J. McCann and R. Pinal "Creating a more effective surrogate compact for roller compaction investigations: Study of the role of shear forces on a compact's properties using near infrared spectroscopy" AAPS, v.10, 2009, p..

F. Boukouvala, F. J. Muzzio, and Marianthi G. Ierapetritou "Dynamic Data-Driven Modeling of Pharmaceutical Processes" Industrial & Engineering Chemistry Research, v.50(11), 2011, p.6743. doi:10.1021/ie102305a 

Gao, Y., Ierapetritou, M. and Muzzio, F. "Investigation on the effect of blade patterns on continuous solid mixing performance" The Canadian Journal of Chemical Engineering, v.89, 2011, p.969.

R.J. McCann and R. Pinal "Creating a more effective surrogate compact for roller compaction investigations: Study of the role of shear forces on a compact's properties using near infrared spectroscopy" The AAPS Journal, v.10(S2), 2009, p..

Gao, Y., Ierapetritou, M. and Muzzio, F. "Periodic section modeling of convective continuous powder mixing processes" AIChE Journal, v., 2011, p..

Gao, Y., Ierapetritou, M. and Muzzio, F. "Investigation on the effect of blade patterns on continuous solid mixing performance" The Canadian Journal of Chemical Engineering, v.89, 2011, p.969. doi:10.1002/cjce.20530 

Gao, Y., Muzzio, F. and Ierapetritou, M. "Characterization of feeder effects on continuous solid mixing using fourier series analysis" AIChE Journal, v.57, 2011, p.1144.

A. Zarow, B. Zhou, X. Wang, R. Pinal and Z. Iqbal "Spectroscopic and X-ray Diffraction Study of Structural Disorder in Cryomilled and Amorphous Griseofulvin" Applied Spectroscopy, v.65, 2011, p.135.

A. Zarow, B. Zhou, X. Wang, R. Pinal and Z. Iqbal "Spectroscopic and X-ray Diffraction Study of Structural Disorder in Cryomilled and Amorphous Griseofulvin" Applied Spectroscopy, v.65, 2011, p.135. doi:10.1366/10-06024 

Dubey, A., Sarkar, A., Ierapetritou, M., Wassgren, C., Muzzio, FJ "Computational Approaches for Studying the Granular Dynamics of Continuous Blending Processes, 1-DEM Based Methods" Macromolecular Materials and Engineering, v.296, 2011, p.290. doi:10.1002/mame.201000389 

P. Sung, Y. Hsieh, K. Angonese, D. Dunn, R.J. King, R. Machbitz, A. Christianson, W.J. Chappell, L.S. Taylor, and M.T. Harris "Complex dielectric properties of microcrystalline cellulose, anhydrous lactose, and alpha-lactose monohydrate powders using a microwave-based open-reflection resonator sensor" J.Pharm.Sci, v.100, 2011, p.2920.

Gao, Y., Muzzio, F. and Ierapetritou, M. "Characterization of feeder effects on continuous solid mixing using fourier series analysis" AIChE Journal, v.57, 2011, p.1144. doi:10.1002/aic.12348 

Gao Y., A. Vanarase, F. J. Muzzio, M. G. Ierapetritou "Characterizing continuous powder mixing using residence time distribution" Chemical Engineering Science, v.66, 2010, p.417.

Zhenya Jia, Eddie Davis, Fernando J. Muzzio and Marianthi G. Ierapetritou "Predictive Modeling for Pharmaceutical Processes Using Kriging and Response Surface" Journal of Pharmaceutical Innovation, v.4, 2009, p.174.

Arun Giridhar, Intan Hamdan, Girish Joglekar, Venkat Venkatasubramanian, Gintaras V. Reklaitis "Real-time process management in particulate and pharmaceutical systems" Computer Aided Process Engr., v.29A, 2011, p.1035.

Gao Y., A. Vanarase, F. J. Muzzio, M. G. Ierapetritou "Characterizing continuous powder mixing using residence time distribution" Chemical Engineering Science, v.66, 2010, p.417. doi:10.1016/j.ces.2010.10.045 

Rafael Mendez, Fernando Muzzio, Carlos Velazquez "Study of the effects of feed frames on powder blend properties during the filling of tablet press dies" Powder Technology, v.200, 2010, p.105.

Zhenya Jia, Eddie Davis, Fernando J. Muzzio and Marianthi G. Ierapetritou "Predictive Modeling for Pharmaceutical Processes Using Kriging and Response Surface" Journal of Pharmaceutical Innovation, v.4, 2009, p.174. doi:10.1007/s12247-009-9070-6 

Mendez, R., Muzzio, F. J. and Velazquez, C. "Powder hydrophobicity and flow properties: Effect of feed frame design and operating parameters" AIChE Journal, v., 2011, p..

Rafael Mendez, Fernando Muzzio, Carlos Velazquez "Study of the effects of feed frames on powder blend properties during the filling of tablet press dies" Powder Technology, v.200, 2010, p.105. doi:10.1016/j.powtec.2010.02.010 

P. Sung, Y. Hsieh, K. Angonese, D. Dunn, R.J. King, R. Machbitz, A. Christianson, W.J. Chappell, L.S. Taylor, and M.T. Harris "Complex dielectric properties of microcrystalline cellulose, anhydrous lactose, and alpha-lactose monohydrate powders using a microwave-based open-reflection resonator sensor" J.Pharm.Sci, v.100, 2011, p.2920. doi:10.1002/jps.22516 

El Hagrasy, A.S., Hennenkamp, J.R., Burke, M.D., Cartwright, J.J. and Litster, J.D. "Twin screw granulation: Influence of formulation parameters on granule properties and growth behavior" Powder Technology, v., 2012, p..

Gao Y., Muzzio F., Ierapetritou M.G. "Optimizing continuous powder mixing processes using periodic section modeling" Chemical Engineering Science, v.80, 2012, p.70.

Boukouvala F., Ierapetritou M, Muzzio F. "Design Space of Pharmaceutical Processes using Data-Driven- Based methods" JOPI, v.5, 2010, p..

Boukouvala, F., Niotis, V., Ramachandran, R.,Muzzio F.,Ierapetritou, M.G. "An integrated approach for dynamic flowsheet modeling andsensitivity analysis of a continuous tablet manufacturing process" Comp. and Chem. Eng., v.42, 2012, p.30.

Boukouvala, F., Ierapetritou, M.G. "Feasibility analysis of black-box processes using an adaptive sampling kriging-based method" Computers and Chemical Engineering, v.36, 2012, p.358.

Kumar, R., Wassgren C. "Angular circulation speed of tablets in a vibratory tablet coating pan" AAPS PharmaSciTech, v., 2012, p..

Arun Giridhar, Intan Hamdan, Girish Joglekar, Venkat Venkatasubramanian, Gintaras V. Reklaitis "Real-time process management in particulate and pharmaceutical systems" Computer Aided Process Engr, v.29A, 2011, p.1035. doi:doi:10.1016/B978-0-444-53711-9.50207-8 

Boukouvala F., Ierapetritou M, Muzzio F. "Design Space of Pharmaceutical Processes using Data-Driven- Based methods" JOPI, v.5, 2010, p.119.

Boukouvala F., Ierapetritou M, Muzzio F. "Design Space of Pharmaceutical Processes using Data-Driven- Based methods" JOPI, v.5, 2010, p.119.

Singh R., Boukouvala F.,Jayjock E.,Ramachandran R.,Ierapetritou M.,Muzzio F. "Flexible Multipurpose Continuous Processing" Pharm Pro Magazine, v., 2012, p..

Fani Boukouvala, Atul Dubey, Aditya Vanarase, Rohit Ramachandran, Fernando J. Muzzio, Marianthi Ierapetritou "Computational Approaches for Studying the Granular Dynamics of Continuous Blending Processes, Part 2 Population Balance and Data-Based Methods" Macromolecular Materials and Engineering, v.9, 2012, p.297.

Gao Y., Muzzio F., Ierapetritou M.G. "A review of the Residence Time Distribution (RTD) applications in solid unit operations" Powder Technology, v., 2012, p..

Gao Y., Muzzio F., Ierapetritou M.G. "Optimizing continuous powder mixing processes using periodic section modeling" Chemical Engineering Science, v.80, 2012, p.70.

Singh, R., Ierapetritou, M., Ramachandran, R. "An engineering study on the enhanced control and operation of continuous manufacturing of pharmaceutical tablets via roller compaction" International Journal of Pharmaceutics, v.438, 2012, p.307.

Boukouvala, F., Niotis, V., Ramachandran, R.,Muzzio F.,Ierapetritou, M.G. "An integrated approach for dynamic flowsheet modeling and sensitivity analysis of a continuous tablet manufacturing process" Comp. and Chem. Eng., v.42, 2012, p.30.

Ramachandran, R., Arjunan, J., Chaudhury, A, Ierapetritou, M. "Model-Based Control Loop Performance Assessment of a Continuous Direct Compaction Pharmaceutical Processes" J. Pharm. Innov., v.6, 2012, p.649.

Singh, R., Boukouvala, F., Jayjock, E., Ramachandran, R. Ierapetritou, M., Muzzio, F. "Flexible Multipurpose Continuous Processing of Pharmaceutical Tablet Manufacturing Process." GMP news, European Compliance Academic (ECE), v., 2012, p..

Fani Boukouvala, Fernando J. Muzzio and Marianthi G. Ierapetritou "Design Space of Pharmaceutical Processes Using Data-Driven-Based Methods" Journal of Pharmaceutical Innovation, v.5, 2010, p.119.

Boukouvala, F., Ierapetritou, M.G. "Feasibility analysis of black-box processes using an adaptive sampling kriging-based method" Computers and Chemical Engineering, v.36, 2012, p.358.

Singh, R., Boukouvala, F., Jayjock, E., Ramachandran, R. Ierapetritou, M., Muzzio, F. "Flexible Multipurpose Continuous Processing." PharmPro Magazine, Pharmaceutical Processing, v., 2012, p..

Fani Boukouvala, Atul Dubey, Aditya Vanarase, Rohit Ramachandran, Fernando J. Muzzio, Marianthi Ierapetritou "Computational Approaches for Studying the Granular Dynamics of Continuous Blending Processes, Part 2 Population Balance and Data-Based Methods" Macromolecular Materials and Engineering, v.9, 2012, p.297. doi:10.1002/mame.201100054 

Boukouvala, F., Gao, Y., Muzzio, F., Ierapetritou, M.G. "Reduced-order discrete element method modeling" Chemical Engineering Science, v.95, 2013, p.12.

Rogers, A.J., Hashemi, A., Ierapetritou, M.G. "Modeling of Particulate Processes for the Continuous Manufacture of Solid-Based Pharmaceutical Dosage Forms" Processes, v.1, 2013, p.67.

Rogers, A.J., Inamdar, C., Ierapetritou, M.G. "An Integrated Approach to Simulation of Pharmaceutical Processes for Solid Drug Manufacture" Ind. Eng. Chem. Res., v., 2013, p..

Sen, M., Rogers, A., Singh, R., Chaudhury, A., John, J., Ierapetritou, M.G., Ramachandran, R. "Flowsheet optimization of an integrated continuous purification-processing pharmaceutical manufacturing operation" Chemical Engineering Science, v.102, 2013, p.56.

D. Barrasso, S. Oka, A. Muliadi, J. D. Litster, C. Wassgren, R. Ramachandran "Population Balance Model Validation and Prediction of CQAs for Continuous Milling Processes: toward QbD in Pharmaceutical Drug Product Manufacturing" Journal of Pharmaceutical Innovation, v.8, 2013, p.147.

D. Barrasso, S. Walia, R. Ramachandran "Multidimensional population balance modeling of continuous granulation processes: a parametric study" Powder Technology, v.241, 2013, p.85.

Xue Liu, Fernando J. Muzzio, Johannes G. Khinast, Benjamin J. Glasser "Fluidized Bed Drying of Pharmaceutical Materials: Moisture Measurement and Effects of Particle Size" American Pharmaceutical Review, v.4, 2013, p..

Fani Boukouvala, Fernando J. Muzzio and Marianthi G. Ierapetritou "Design Space of Pharmaceutical Processes Using Data-Driven-Based Methods" Journal of Pharmaceutical Innovation, v.5, 2010, p.119. doi:10.1007/s12247-010-9086-y 

A.S. El Hagrasy, J. Hennenkamp, M. Burke, J. Cartwright and J.D. Litster "Twin Screw Granulation: Influence of Formulation Parameters on Granule Properties and Growth Behaviour" Powder Technology, v., 2013, p..

El Hagrasy, A, Litster, JD "Granulation Rate Processes in the Kneading Elements of a Twin Screw Granulator" AIChE J, v., 2013, p..

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