title: Oral dosage form performance tests: new dissolution approaches.
abstract: The performance test is one of a series of tests that compose the specification in a United States Pharmacopeia (USP) dosage form monograph. For an orally administered, nonsolution dosage form, it is usually satisfied by either a dissolution or disintegration procedure. Dissolution acceptance criteria are usually set in private negotiations between an applicant and a regulatory agency. With information about this private agreement and other information provided in a sponsor's Request for Revision to USP, the USP's Council of Experts elaborates a public dosage form monograph. Based on the relationship between the regulatory decisions and the Request for Revision, the USP dissolution procedure links to a regulatory judgment about bioavailability and bioequivalence and, ultimately, to a judgment about safety and efficacy. The current dissolution procedure and acceptance criteria are perceived as having worked well over the years and are generally accepted. This article discusses new approaches that merit consideration. These approaches focus on a) explicit use of hypothesis testing, b) use of parametric tolerance intervals, c) improved ways to set dissolution acceptance criteria, and d) a more flexible protocol to assess conformity. Application of the proposed approaches may better assess, manage, and communicate both manufacturer and consumer risk for dissolution testing.
authors.affiliation: Biostatistics Section, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Walter W
authors.initials: WW
authors.lastname: Hauck
authors.forename: Thomas
authors.initials: T
authors.lastname: Foster
authors.forename: Eric
authors.initials: E
authors.lastname: Sheinin
authors.forename: Todd
authors.initials: T
authors.lastname: Cecil
authors.forename: William
authors.initials: W
authors.lastname: Brown
authors.forename: Margareth
authors.initials: M
authors.lastname: Marques
authors.forename: Roger L
authors.initials: RL
authors.lastname: Williams
mesh_terms: D000284:Administration, Oral; D004304:Dosage Forms / Q000592:standards*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends
chemical_list: D004304:Dosage Forms