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
Design and Characterization of a New Miniaturized Rotating Disk Equipment for In Vitro Dissolution Rate Studies
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Inst för kemi, Göteborgs universitet.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
AstraZeneca, Mölndal.
Show others and affiliations
2008 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 97, no 8, 3344-3355 p.Article in journal (Refereed) Published
Abstract [en]

A miniaturized apparatus for the determination of the apparent in vitro dissolution rate has been designed, constructed and characterized. The miniaturized apparatus was based on a low volume dissolution cell and a disk in a rotating magnetic bar. The disk tablet is pressed directly into the bar with a press designed and constructed for this purpose. It requires approximately 5 mg of substance. The disk was positioned eccentrically on the bar with an external flow of medium to increase the rate of solvent flow over the disk surface. Six different drug substances were used. The dissolution media were sodium phosphate buffer, pH 7.0, and ammonium acetate buffer, pH 6.8. All quantifications were made by integrating the dissolution cell with high-performance liquid chromatography (HPLC) using diode-array detection (DAD). The obtained results were compared with data from a conventional rotating disk equipment, where the disk was centrically mounted. The dissolution rates at 100 rpm seemed to be on an average of 2-3 times higher for the miniaturized apparatus (RSD 0.2-56%). The preliminary studies of this prototype indicate that the miniaturized rotating disk is a promising design for the qualitative estimation of dissolution rates of substances, for example during screening in early drug discovery.

Place, publisher, year, edition, pages
Wiley InterScience , 2008. Vol. 97, no 8, 3344-3355 p.
Keyword [en]
dissolution rate, in vitro models, physicochemical properties; analytical chemistry, HPLC (high-performance/pressure liquid chromatography), miniaturization
National Category
Medicinal Chemistry Medicinal Chemistry
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-17637DOI: 10.1002/jps.21235ISI: 000258081100034OAI: oai:DiVA.org:uu-17637DiVA: diva2:45408
Available from: 2010-01-11 Created: 2009-10-08 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Evaluation of a Miniaturized Rotating Disk Apparatus for In Vitro Dissolution Rate Measurements in Aqueous Media: Correlation of In Vitro Dissolution Rate with Apparent Solubility
Open this publication in new window or tab >>Evaluation of a Miniaturized Rotating Disk Apparatus for In Vitro Dissolution Rate Measurements in Aqueous Media: Correlation of In Vitro Dissolution Rate with Apparent Solubility
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The general aim of this thesis was to evaluate a newly designed and constructed miniaturized rotating disk apparatus for in vitro dissolution rate measurements of different drug substances from all of the classes in the Biopharmaceutical Classification System (BCS). The new equipment is based on a low volume flow-through cell of Plexiglas, a gold plated magnetic bar and a special designed press. The disk of drug substance (approx. 5 mg) is placed eccentrically in the bar. Rotation speeds were set with a graded magnetic stirrer. An external HPLC pump delivered a continuous flow of aqueous medium to the flow-through cell during dissolution testing.

A reversed phase high-performance liquid chromatography system using diode array detection (RP-HPLC-DAD) was coupled online to the new equipment. The injections from the miniaturized rotating disk outlet into the quantifying HPLC system were controlled by a six-position switching valve. The injection volumes from the valve and the autosampler, used for the external standards, were statistically evaluated to match each other volumetrically. No analyses were longer than three minutes, using isocratic mode.

A traditional USP rotating disk apparatus was used as a reference system and the two instruments were shown to be statistically dissimilar in the numerical dissolution rate values probably due to different hydrodynamics, but had approximately the same precision/repeatability. When correlating the logarithmic values of the in vitro dissolution rate (G) with the apparent solubility (S), using shake-flask methodology in the solubility studies, the two apparatuses gave the same correlation patterns. Further correlation studies were done where the media components were altered by the use of different buffer species or additives into the buffers, such as inorganic salts.

Chemometric tools, e.g. orthogonal partial least squares (OPLS), were used to better evaluate the most influential factors for G and S in different media. The most significant factor for a model basic drug substance (terfenadine) was pH, followed by the ionic strength (I) and added sodium chloride in one of the media. However, the surfactants in the Fasted State Simulated Intestinal Fluid (FaSSIF-V2) were found to be insignificant for G and S in this study (using a 95% confidence interval).

The new miniaturized apparatus is a promising prototype for in vitro dissolution rate measurements both for early screening purposes and in dissolution testing during drug development, but needs further instrumental improvements.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 118
Keyword
analytical methods, HPLC (high-performance liquid chromatography), miniaturization, in vitro dissolution rate, apparent solubility, physicochemical properties, dissolution media, correlation study, chemometrics
National Category
Medicinal Chemistry
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
urn:nbn:se:uu:diva-112257 (URN)978-91-554-7708-0 (ISBN)
Public defence
2010-02-26, B22, BMC (Uppsala Biomedicinska Centrum), Dag Hammarskjöldsväg/Husargatan, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2010-02-04 Created: 2010-01-12 Last updated: 2010-02-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full texthttp://www3.interscience.wiley.com/journal/117935713/grouphome/home.html

Authority records BETA

Persson, Anita M.Sundelöf, Lars-OlofPettersson, Curt

Search in DiVA

By author/editor
Persson, Anita M.Sundelöf, Lars-OlofPettersson, Curt
By organisation
Analytical Pharmaceutical ChemistryOrganic Pharmaceutical Chemistry
In the same journal
Journal of Pharmaceutical Sciences
Medicinal ChemistryMedicinal Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 422 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