title: Application of a Stable Isotope Approach to Evaluate Impact of Changes in Manufacturing Parameters for an Immediate-Release Tablet.
abstract: There is continued emphasis from the various worldwide regulatory agencies to ensure that the pharmaceutical industry fully understands the products they are developing. This emphasis is seen via development of quality-by-design (QbD) publications and guidelines generated by the International Committee on Harmonization. The challenge to meet these expectations is primarily associated with the generation of in vivo data (eg, pharmacokinetic data) that is resource intensive. A technique reducing the resources needed to generate this in vivo data permits a more extensive application of QbD principles. This paper presents the application of stable isotopes in pharmacokinetic studies. The data show that the use of stable isotopes can significantly reduce the number of subjects required for a study. This reduction in subjects thus translates into a significant reduction in resources and time needed to generate the required in vivo data to support QbD.
authors.affiliation: BioCeutics LLC, Emerald Isle, NC, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Parr
authors.affiliation: GlaxoSmithKline, Inc, Stevenage, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Badman
authors.affiliation: GlaxoSmithKline, Inc, King of Prussia, PA, USA.
authors.forename: Chester L
authors.initials: CL
authors.lastname: Bowen
authors.affiliation: Ocera Therapeutics, Inc, Durham, NC, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Coffin
authors.affiliation: GlaxoSmithKline, Inc, Collegeville, PA, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Roivant Sciences, Inc, Durham, NC, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Jones
authors.affiliation: GlaxoSmithKline, Inc, King of Prussia, PA, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Kurtinecz
authors.affiliation: Chimerix, Inc, Durham, NC, USA.
authors.forename: Odin
authors.initials: O
authors.lastname: Naderer
authors.affiliation: GlaxoSmithKline, Inc, Collegeville, PA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Travis
authors.affiliation: GlaxoSmithKline, Inc, King of Prussia, PA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Zhu
authors.affiliation: GlaxoSmithKline, Inc, Research Triangle Park, NC, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Patel
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D013607:Tablets
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D004041:Dietary Fats; C583947:GSK1322322; D006877:Hydroxamic Acids; D013607:Tablets
keywords: quality by design; relative bioavailability; stable isotope