uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Investigation of the Intra- and Interlaboratory Reproducibility of a Small Scale Standardized Supersaturation and Precipitation Method
Univ Copenhagen, Dept Pharm, Copenhagen, Denmark..ORCID iD: 0000-0002-8148-8129
Univ Copenhagen, Dept Pharm, Copenhagen, Denmark.;Analyt Res & Dev, H Lundbeck A-S,Ottiliavej 9, DK-2500 Valby, Denmark..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Johnson & Johnson, Janssen Pharmaceut, Pharmaceut Sci, Beerse, Belgium.
Show others and affiliations
2017 (English)In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 14, no 12, p. 4161-4169Article in journal (Refereed) Published
Abstract [en]

The high number of poorly water-soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g., the small intestine, increasing the amount of dissolved compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation. Therefore, an in vitro method is needed, from where the ability of a compound to supersaturate can be defined in a reproducible way. Hence, this study investigates the reproducibility of an in vitro small scale standardized supersaturation and precipitation method (SSPM). First an intralaboratory reproducibility study of felodipine was conducted, after which seven partners contributed with data for three model compounds; aprepitant, felodipine, and fenofibrate, to determine the interlaboratory reproducibility of the SSPM. The first part of the SSPM determines the apparent degrees of supersaturation (aDS) to investigate for each compound. Each partner independently determined the maximum possible aDS and induced 100, 87.5, 75, and 50% of their determined maximum possible aDS in the SSPM. The concentration time profile of the supersaturation and following precipitation was obtained in order to determine the induction time (t(ind)) for detectable precipitation. The data showed that the absolute values of t(ind) and aDS were not directly comparable between partners, however, upon linearization of the data a reproducible rank ordering of the three model compounds was obtained based on the beta-value, which was defined as the slope of the In(t(ind)) versus In(aDS)(-2) plot. Linear regression of this plot showed that aprepitant had the highest beta-value, 15.1, while felodipine and fenofibrate had comparable beta-values, 4.0 and 4.3, respectively. Of the five partners contributing with full data sets, 80% could obtain the same rank order for the three model compounds using the SSPM (aprepitant > felodipine approximate to fenofibrate). The alpha-value is dependent on the experimental setup and can be used as a parameter to evaluate the uniformity of the data set. This study indicated that the SSPM was able to obtain the same rank order of the beta-value between partners and, thus, that the SSPM may be used to classify compounds depending on their supersaturation propensity.

Place, publisher, year, edition, pages
2017. Vol. 14, no 12, p. 4161-4169
Keywords [en]
supersaturation, precipitation, oral drug delivery, variability
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science
Identifiers
URN: urn:nbn:se:uu:diva-339902DOI: 10.1021/acs.molpharmaceut.7b00419ISI: 000417342400005PubMedID: 29043811OAI: oai:DiVA.org:uu-339902DiVA, id: diva2:1176973
Available from: 2018-01-23 Created: 2018-01-23 Last updated: 2018-03-08Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Teleki, AlexandraBergström, Christel

Search in DiVA

By author/editor
Plum, JakobTeleki, AlexandraBergström, ChristelMullertz, Anette
By organisation
Department of Pharmacy
In the same journal
Molecular Pharmaceutics
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 19 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf