Advancing Unit Operations for Continuous Processing in Solid-Dosage Manufacturing - Pharmaceutical Technology

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Advancing Unit Operations for Continuous Processing in Solid-Dosage Manufacturing
The article examines some recent developments for this process step and for continuous manufacturing overall. This article is part of a special issue on solid dosage and excipients.


Pharmaceutical Technology
Volume 36, Issue 3, pp. s18-s20

Academic–industrial partnerships

Continuous manufacturing also is being advanced by industrial, public, and academic partnerships. For example, in October 2011, FDA awarded a $35-million, five-year grant to the National Institute for Pharmaceutical Technology and Education (NIPTE), a nonprofit research center focused on pharmaceutical product development and manufacturing, to improve drug manufacturing standards. NIPTE's goal is to increase science and engineering-based understanding, so technologies can be developed and science-based regulations can be implemented. The FDA grant will in part by used to promote continuous manufacturing as well as other issues, such as improving small-batch production, reducing the environmental impact of manufacturing pharmaceutical products, and rectifying other drug-development and manufacturing problems.

NIPTE is partnered with 10 US universities involved in the pharmaceutical sciences and engineering. The member universities are Duquesne University, the Illinois Institute of Technology, Purdue University, Rutgers University, the University of Puerto Rico, the University of Connecticut, the University of Iowa, the University of Kentucky, the University of Maryland–Baltimore, and the University of Minnesota.

In April 2011, the United Kingdom's Engineering and Physical Sciences Research Council (EPSRC) established the EPSRC Center for Innovative Manufacturing in Continuous Manufacturing and Crystallization. EPSRC is the main UK government agency for funding research and training in engineering and the physical sciences. The University of Strathclyde is leading the EPSRC Center for Innovative Manufacturing in Continuous Manufacturing and Crystallization, which also involves the Universities of Bath, Cambridge, Edinburgh, Glasgow, Heriot-Watt, and Loughborough. Industry partners include GlaxoSmithKline, Pfizer, AstraZeneca, Fujifilm, Croda, Genzyme (now part of Sanofi), NiTech Solutions, Phoenix Chemicals, Solid Form Solutions, and British Salt.

The EPSRC Center for Innovative Manufacturing in Continuous Manufacturing and Crystallization has identified several key research challenges:

  • Achieving precise control over manufacturing of solid particles using continuous-manufacturing technologies
  • Understanding the control of nucleation and growth of particles by means of crystallization under continuous flow
  • Developing continuous crystallization platforms, process analysis tools, and strategies to manufacture particles for different applications
  • Delivering the tools to control crystal structure, particle shape, and particle-size distribution
  • Facilitating continuous manufacture of medicines and nanomaterials with kinetic, cocrystallization, and impurity control (5).

In 2007, Novartis formed a $65-million, 10-year research collaboration with the Massachusetts Institute of Technology (MIT) to launch and fund the Novartis–MIT Center for Continuous Manufacturing to develop new technologies to replace the pharmaceutical industry's conventional batch-based system with continuous manufacturing processes.

The Engineering Research Center For Structure Organic Particulate Systems, a multi-university consortium consisting of Rutgers University, Purdue University, the New Jersey Institute of Technology, and the University of Puerto Rico at Mayagüez, is another academic-partnership involved in continuous processing. The center, which is funded by National Science Foundation and industrial partners, includes 35 pharmaceutical manufacturers and equipment producers involved in R&D for continuous processing (2).

Researchers at Rutgers University recently reported on an enhanced model-based control of a continuous direct-compression pharmaceutical process. The control-loop performance was assessed in silico, and results obtained will be incorporated into the pilot-plant facility of the continuous direct-compaction process at the National Science Foundation's Engineering Research Center at Rutgers University. The models used in the study were obtained by means of a system identification from a combination of first principles-based dynamic models, experimental data, and/or literature data. The purpose of the study was to formulate an effective control strategy at the basic/regulatory level for the integrated continuous operation of the direct-compaction process and to maintain the process at the desired set-points, taking into account the multivariable process interactions and disturbances (6).

References

1. B.L. Trout et al., Ind. Eng. Chem. Res. 50 (17), 10083–10092 (2011).

2. P. Van Arnum and R. Whitworth, Pharm. Technol. 35 (9), 44–47 (2011).

3. M. Fonteyne et al., "Real-time Assessment of Critical Quality Attributes of a Continuous Granulation Process," Pharm. Develop. & Technol., online, DOI 10.3109/10837450.2011.627869, Oct. 24. 2011.

4. L. Tan et al., Pharm. Develop. & Technol. 16 (4), 302–305 (2011).

5. EPSRC, "EPSRC Center for Innovative Manufacturing in Continuous Manufacturing and Crystallization," http://www.epsrc.ac.uk/funding/centres/innovativemanufacturing/Pages/imrccontinuousmanufacturing.aspx, accessed Feb. 13, 2012.

6. R. Ramachandran et al. , J. Pharm. Innov. 6 (4), 249–263 (2011).


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