title: Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for preformulation.
abstract: This study describes a novel Miniaturized INtrinsic DISsolution Screening (MINDISS) assay for measuring disk intrinsic dissolution rates (DIDR). In MINDISS, compacted mini disks of drugs (2-5mg/disk) are prepared in custom made holders with a surface area of 3mm(2). Disks are immersed, pellet side down, into 0.35ml of appropriate dissolution media per well in 96-well microtiter plates, media are stirred and disk-holders are transferred to new wells after defined periods of time. After filtration, drug concentration in dissolution media is quantified by Ultra Performance Liquid Chromatography (UPLC) and solid state property of the disk is characterized by Raman spectroscopy. MINDISS was identified as an easy-to-use tool for rapid, parallel determination of DIDR of compounds that requires only small amounts of compound and of dissolution medium. Results obtained with marketed drugs in MINDISS correlate well with large scale DIDR methods and indicate that MINDISS can be used for (1) rank-ordering of compounds by intrinsic dissolution in late phase discovery and early development, (2) comparison of polymorphic forms and salts, (3) screening and selection of appropriate dissolution media, and (4) characterization of the intestinal release behavior of compounds along the gastro intestinal tract by changing biorelevant media during experiments.
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pre-Clinical CMC, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel, Switzerland. Electronic address: jochem.alsenz@roche.com.
authors.forename: Jochem
authors.initials: J
authors.lastname: Alsenz
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pre-Clinical CMC, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel, Switzerland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Haenel
authors.affiliation: Pharma Technical Development Quality Systems (PTDQS), F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Bldg. 065/418A, Basel CH 4070, Switzerland.
authors.forename: Aline
authors.initials: A
authors.lastname: Anedda
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pre-Clinical CMC, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel, Switzerland.
authors.forename: Pauline
authors.initials: P
authors.lastname: Du Castel
authors.affiliation: Roche Pharmaceutical Research & Early Development, Pre-Clinical CMC, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel, Switzerland.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cirelli
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D065546:Drug Liberation; D008904:Miniaturization; D004364:Pharmaceutical Preparations / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations
keywords: Intrinsic dissolution; Pharmaceutical profiling; Polymorphs; Preformulation; Ranking of drugs; Salts; Small scale