Melt Extrusion pp 435-445 | Cite as

Consistency of Pharmaceutical Products: An FDA Perspective on Hot-Melt Extrusion Process

Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 9)

Abstract

Hot-melt extrusion represents an efficient technology to formulate drugs with poor aqueous solubility into safe and effective drug delivery systems. The interest in this technology continues to grow as it is suitable for both high dose and potent low dose compounds. It is amenable to real-time monitoring and control of the consistency of the product with respect to content uniformity and crystalline conversion. Quality-by-design (QbD) has become an essential part of modern pharmaceutical quality systems since it incorporates an enhanced product and process understanding. It encourages real-time monitoring and control of critical material attributes and process parameters. The QbD paradigm can be easily incorporated into hot-melt processes. It has the potential to replace traditional batch processes due to its continuous nature and ease of scale-up from laboratory scale to commercial scale.

Keywords

Permeability Crystallization Toxicity Europe Recrystallization 

Notes

Disclaimer

The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

References

  1. Applications for FDA Approval to Market a New Drug, Title 21 Code of Federal Regulations. Pt 314. 2012 ed. Available:http://www.gpo.gov/; Accessed: 02/02/2013.
  2. Baert L, Verreck G (2006) Antiviral compositions. US Patent 7,887,845, 3 Feb 2006Google Scholar
  3. Federal Food, Drug, and Cosmetic Act, Title 21 U.S. Code. 2006 ed. Suppl V, 2011. Available: http://www.gpo.gov/; Accessed: 02/02/2013.
  4. Fort JJ, Krill SL, Law D, QiuPorter Y, Porter WR, Schmitt EA (2000) Solid dispersion pharmaceutical formulations. US Patent 7,364,752, 10 Nov 2000Google Scholar
  5. Gryczke A, Schminke S, Maniruzzaman M, Beck J, Douroumis D (2011) Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion. Colloids Surf B Biointerfaces 86:275–284PubMedCrossRefGoogle Scholar
  6. ICH Harmonised Tripartite Guideline (1999) ICH Q6A: specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substancesGoogle Scholar
  7. ICH Harmonised Tripartite Guideline (2005) ICH Q9: quality risk managementGoogle Scholar
  8. ICH Harmonised Tripartite Guideline (2008) ICH Q10: pharmaceutical quality systemGoogle Scholar
  9. ICH Harmonised Tripartite Guideline (2009) ICH Q8 (R2): pharmaceutical developmentGoogle Scholar
  10. International Conference on Harmonisation (1999). Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances. Q6A. 1999.http://www.ich.org/; Accessed: 02/01/2013.
  11. International Conference on Harmonisation (2005). Quality Risk Management. Q9.http://www.ich.org/; Accessed: 02/01/2013.
  12. International Conference on Harmonisation (2008). Pharmaceutical Quality System. Q10.http://www.ich.org/; Accessed: 02/01/2013.
  13. International Conference on Harmonisation (2009). Pharmaceutical Development. Q8(R2).http://www.ich.org/; Accessed: 02/01/2013.
  14. Klein CE, Chiu YL, Awni W, Zhu T, Heuser RS, Doan T, Breitenbach J, Morris JB, Brun SC, Hanna GJ (2007) The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect. J Acquir Immune Defic Syndr 44:401–410PubMedCrossRefGoogle Scholar
  15. Maniruzzaman M, Boateng JS, Bonnefille M, Aranyos A, Mitchell JC, Douroumis D (2012) Taste masking of paracetamol by hot-melt extrusion: an in vitro and in vivo evaluation. Eur J Pharm Biopharm 80:433–442PubMedCrossRefGoogle Scholar
  16. Repka MA, Battu SK, Upadhye SB, Thumma S, Crowley MM, Zhang F, Martin C, McGinity JW (2007) Pharmaceutical applications of hot-melt extrusion: part II. Drug Dev Ind Pharm 33:1043–1057PubMedCrossRefGoogle Scholar
  17. Saerens L, Dierickx L, Lenain B, Vervaet C, Remon JP, De Beer T (2011) Raman spectroscopy for the in-line polymer-drug quantification and solid state characterization during a pharmaceutical hot-melt extrusion process. Eur J Pharm Biopharm 77:158–163PubMedCrossRefGoogle Scholar
  18. Saerens L, Dierickx L, Quinten T, Adriaensens P, Carleer R, Vervaet C, Remon JP, De Beer T (2012) In-line NIR spectroscopy for the understanding of polymer-drug interaction during pharmaceutical hot-melt extrusion. Eur J Pharm Biopharm 81:230–237PubMedCrossRefGoogle Scholar
  19. Title 21, Code of Federal Regulations, Part 314. Sec 314.94(a)(9)(ii). 2012 edGoogle Scholar
  20. Title 21 UStateC, Chapter 9—Federal Food, Drug, and Cosmetic Act. 2012 edGoogle Scholar
  21. Tumuluri SV, Prodduturi S, Crowley MM, Stodghill SP, McGinity JW, Repka MA, Avery BA (2004) The use of near-infrared spectroscopy for the quantitation of a drug in hot-melt extruded films. Drug Dev Ind Pharm 5:505–511CrossRefGoogle Scholar
  22. Tumuluri VS, Kemper MS, Lewis IR, Prodduturi S, Majumdar S, Avery BA, Repka MA (2008) Off-line and on-line measurements of drug-loaded hot-melt extruded films using Raman spectroscopy. Int J Pharm 357:77–84PubMedCrossRefGoogle Scholar
  23. US Food and Drug Administration (2000) Guidance for Industry. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification SystemGoogle Scholar
  24. US Food and Drug Administration (2004) Guidance for Industry. PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality AssuranceGoogle Scholar
  25. US Food and Drug Administration (2005) Guidance for Industry. Nonclinical Studies for the Safety Evaluation of Pharmaceutical ExcipientsGoogle Scholar
  26. US Food and Drug Administration (2012) Inactive Ingredients Database.http:/www.accessdata.fda.gov/scripts/cder/iig/index.cfm; Accessed: 02/01/2013
  27. Zajc N, Srčič S (2004) Binary melting phase diagrams of nifedipine-PEG 4000 and nifedipine-mannitol systems. J Therm Anal Cal 77:571–580CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.Division of Product Quality Research, Office of Pharmaceutical ScienceUS Food and Drug AdministrationSilver SpringUSA

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