Abstract
In vitro dissolution testing is an important tool used for development and approval of generic dosage forms. The objective of this article is to summarize how dissolution testing is used for the approval of safe and effective generic drug products in the United States (US). Dissolution testing is routinely used for stability and quality control purposes for both oral and non-oral dosage forms. The dissolution method should be developed using an appropriate validated method depending on the dosage form. There are several ways in which dissolution testing plays a pivotal role in regulatory decision-making. It may be used to waive in vivo bioequivalence (BE) study requirements, as BE documentation for Scale Up and Post Approval Changes (SUPAC), and to predict the potential for a modified-release (MR) drug product to dose-dump if co-administered with alcoholic beverages. Thus, in vitro dissolution testing plays a major role in FDA’s efforts to reduce the regulatory burden and unnecessary human studies in generic drug development without sacrificing the quality of the drug products.
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REFERENCES
Siewert M, Dressman J, Brown CK, Shah VP. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech. 2003;4(1):1.
Shah VP, Tymes NW, Skelly JP. In vitro release profile of clonidine transdermal therapeutic systems and scopolamine patches. Pharm Res. 1989;6:346–51.
Food and Drug Administration. Guidance for industry: immediate release solid oral dosage forms: scale-up and post-approval changes. Rockville, MD: US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; November 1995.
Food and Drug Administration. Guidance for industry: modified release solid oral dosage forms: scale-up and post-approval changes. Rockville, MD: US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; October 1997.
Chapter 711: Dissolution. In: United States Pharmacopeia 31 (USP 31): National Formulary 26 (NF 26). 2008. p. 267–274. 2010.
Chapter 724: Drug release. In: United States Pharmacopeia 31 (USP 31): National Formulary 26 (NF 26). 2008. p. 275–278. 2010.
Chapter 1092: The dissolution procedure. Development and validation. In: United States Pharmacopeia 31 (USP 31): National Formulary 26 (NF 26). 2008. p. 573–678.
Food and Drug Administration. Guidance for industry: dissolution testing of Immediate Release Solid Oral Dosage Forms. Rockville, MD: US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; August 1997.
Food and Drug Administration. Guidance for industry: bioavailability and bioequivalence studies for orally administered drug products—general considerations. Rockville, MD: US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; March 2003.
Anand O. Dissolution testing: an FDA perspective; AAPS workshop, physical pharmacy and biopharmaceutics. May 5–13, 2009. Baltimore, MD. In: http://mediaserver.aapspharmaceutica.com/meetings/09_PPB/Wed/Track_I/Om_Anand.pdf. Accessed 26 September 2010.
Food and Drug Administration. Guidance for industry: waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Rockville, MD: US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; August 2000.
Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–20.
Individual Product Bioequivalence Recommendations: In: US FDA. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm075207.htm. Accessed 06 October 2010.
FDA Alert for Healthcare Professionals (July 2005): Hydromorphone Hydrochloride Extended-Release Capsules (marketed as Palladone™). 2005 July: http://www.fda.gov/cder/drug/InfoSheets/HCP/hydromorphoneHCP.pdf. Accessed 04 October 2010.
Chandaroy P, Jiang X, Lee C, Thompson C, Conner DP, Davit BM. In vitro alcohol-induced dose-dumping dissolution studies of generic modified-release oral drug products: American Association of Pharmaceutical Scientists 2008 annual meeting, Atlanta, November 2008: http://www.aapsj.org/abstracts/AM_2008/AAPS2008-001832.PDF. Accessed 20 February 2011.
FDA/CDER to Osmotica Pharmaceutical Corp. - petition partial approval and denial. In: http://www.regulations.gov/search/Regs/home.html#docketDetail?R=FDA-2009-P-0403. Accessed 6 October 2010.
FDA/Associate Commissioner for Policy and Planning - petition approval. Docket ID:FDA-2005-P-0366. In: http://www.regulations.gov/search/Regs/home.html#documentDetail?R=090000648044af45. Accessed 07 October 2010.
Kefauver-Harris Amendments. Public Law (PL) 87–781, 87th Congress. 10-10-1962.
Drug Efficacy Study: a report to the commissioner of Food and Drugs, National Academy of Sciences, National Research Council, Washington, DC, 1969.
Conner DP, Davit BM. Bioequivalence and drug product assessment, in vivo. In: Shargel L, Kanfer I, editors. Generic drug product development, solid oral dosage forms. Marcel Dekker, Inc: 2005. p 227–55.
Orange book: In:http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079068.htm#Therapeutic%20Equivalence-Related%20Terms. Accessed 06 October 2010.
Abdou HM. Dissolution. Remington: the science and practice of pharmacy. Nineteenth ed. Mack Publishing Company; 1995. p. 593–604.
Azarmi S, Roa W, Lobenberg R. Current perspectives in dissolution testing of conventional and novel dosage forms. Int J Pharm. 2007;328:12–21.
Chewing gum, medicated, drug release. European Pharmacopoeia, Edition 4. Strasbourg, France: Directorate for the quality of medicines of the Council of Europe; 2002. p. 227–228.
Food and Drug Administration. Guidance for industry: nonsterile semisolid dosage forms: scale-up and post-approval changes. Rockville: US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; 1997.
Zhang H, Yu LX. Dissolution testing for solid oral drug products: theoretical considerations. Am Pharm Rev. 2004;7(5):26–31.
ACKNOWLEDGMENTS
The authors would like to thank Dr. Xiaojian Jiang for her valuable suggestions.
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Anand, O., Yu, L.X., Conner, D.P. et al. Dissolution Testing for Generic Drugs: An FDA Perspective. AAPS J 13, 328–335 (2011). https://doi.org/10.1208/s12248-011-9272-y
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DOI: https://doi.org/10.1208/s12248-011-9272-y