Consistency of Pharmaceutical Products: An FDA Perspective on Hot-Melt Extrusion Process
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.
KeywordsDrug Product Solid Dispersion Biopharmaceutics Classification System Process Analytical Technology Fault Tree Analysis
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.
- 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.
- Baert L, Verreck G (2006) Antiviral compositions. US Patent 7,887,845, 3 Feb 2006Google Scholar
- 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.
- 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
- ICH Harmonised Tripartite Guideline (1999) ICH Q6A: specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substancesGoogle Scholar
- ICH Harmonised Tripartite Guideline (2005) ICH Q9: quality risk managementGoogle Scholar
- ICH Harmonised Tripartite Guideline (2008) ICH Q10: pharmaceutical quality systemGoogle Scholar
- ICH Harmonised Tripartite Guideline (2009) ICH Q8 (R2): pharmaceutical developmentGoogle Scholar
- 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.
- International Conference on Harmonisation (2005). Quality Risk Management. Q9.http://www.ich.org/; Accessed: 02/01/2013.
- International Conference on Harmonisation (2008). Pharmaceutical Quality System. Q10.http://www.ich.org/; Accessed: 02/01/2013.
- International Conference on Harmonisation (2009). Pharmaceutical Development. Q8(R2).http://www.ich.org/; Accessed: 02/01/2013.
- 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
- Title 21, Code of Federal Regulations, Part 314. Sec 314.94(a)(9)(ii). 2012 edGoogle Scholar
- Title 21 UStateC, Chapter 9—Federal Food, Drug, and Cosmetic Act. 2012 edGoogle Scholar
- 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
- US Food and Drug Administration (2004) Guidance for Industry. PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality AssuranceGoogle Scholar
- US Food and Drug Administration (2005) Guidance for Industry. Nonclinical Studies for the Safety Evaluation of Pharmaceutical ExcipientsGoogle Scholar
- US Food and Drug Administration (2012) Inactive Ingredients Database.http:/www.accessdata.fda.gov/scripts/cder/iig/index.cfm; Accessed: 02/01/2013