title: Dissolution Failure of Solid Oral Drug Products in Field Alert Reports.
abstract: From 2005 to 2014, 370 data entries of dissolution failures of solid oral drug products were assessed with respect to the solubility of drug substances, dosage forms [immediate release (IR) vs. modified release (MR)], and manufacturers (brand name vs. generic). The study results show that the solubility of drug substances does not play a significant role in dissolution failures; however, MR drug products fail dissolution tests more frequently than IR drug products. When multiple variables were analyzed simultaneously, poorly water-soluble IR drug products failed the most dissolution tests, followed by poorly soluble MR drug products and very soluble MR drug products. Interestingly, the generic drug products fail dissolution tests at an earlier time point during a stability study than the brand name drug products. Whether the dissolution failure of these solid oral drug products has any in vivo implication will require further pharmacokinetic, pharmacodynamic, clinical, and drug safety evaluation. Food and Drug Administration is currently conducting risk-based assessment using in-house dissolution testing, physiologically based pharmacokinetic modeling and simulation, and post-market surveillance tools. At the meantime, this interim report will outline a general scheme of monitoring dissolution failures of solid oral dosage forms as a pharmaceutical quality indicator.
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Dajun
authors.initials: D
authors.lastname: Sun
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Meng
authors.initials: M
authors.lastname: Hu
authors.affiliation: Office of Surveillance, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Mark
authors.initials: M
authors.lastname: Browning
authors.affiliation: Office of Manufacturing Quality, Office of Compliance, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Rick L
authors.initials: RL
authors.lastname: Friedman
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Wenlei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland 20993. Electronic address: Hong.Wen@fda.hhs.gov.
authors.forename: Hong
authors.initials: H
authors.lastname: Wen
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000592:standards; D065546:Drug Liberation; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations
keywords: dissolution; oral drug delivery; solid dosage form; solubility; stability