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Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Janssen Pharmaceut, Pharmaceut Sci, B-2340 Beerse, Belgium.
Sanofi Aventis Rech Dev, Chem & Pharmaceut Anal, F-34184 Montpellier, France.
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2016 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 105, no 9, 2864-2872 p.Article in journal (Refereed) Epub ahead of print
Abstract [en]

The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp > 1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.

Place, publisher, year, edition, pages
2016. Vol. 105, no 9, 2864-2872 p.
Keyword [en]
dissolution; intrinsic dissolution rate; apparent solubility; preformulation; poorly water-soluble drug; small scale
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-288000DOI: 10.1016/j.xphs.2016.03.010ISI: 000381770600043PubMedID: 27112289OAI: oai:DiVA.org:uu-288000DiVA: diva2:923708
Available from: 2016-04-27 Created: 2016-04-27 Last updated: 2016-09-15Bibliographically approved

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Andersson, Sara B. E.Alvebratt, CarolineEdueng, KhadijahBergström, Christel A. S.
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