Dissolution enhancement of griseofulvin from griseofulvin-sodium dodecyl sulfate discs investigated by UV imaging Peter Madelung a , Poul Bertelsen b , Jette Jacobsen a , Anette Müllertz a, c , Jesper Østergaard a, * a Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark b Takeda GmbH, Robert Bosch Strasse 8, 78224 Singen, Germany c Bioneer:Farma, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen, Denmark article info Article history: Received 9 April 2017 Received in revised form 15 May 2017 Accepted 16 May 2017 Available online 17 May 2017 Keywords: Dissolution enhancement Dissolution imaging Griseofulvin Poorly soluble drugs Surfactant UV imaging abstract The purpose of study was to investigate the dissolution rate enhancement obtained when sodium dodecyl sulfate (SDS) is co-compressed with griseofulvin into discs using a UV imaging-based flow- through dissolution testing setup. Griseofulvin dissolution rates obtained from discs containing 5.92 and 10.6% (w/w) SDS in phosphate buffer (pH 6.5) were similar to dissolution rates from pure griseofulvin discs when applying 20 and 100 mM SDS as dissolution medium, respectively. Dynamic light scattering of effluent samples revealed nanosized particles (approximately 135 nm in diameter) escaping the discs during dissolution. Scanning electron microscopy of co-compressed griseofulvin-SDS discs prior to dissolution testing showed surfaces apparently consisting of granules (100 and 200 nm in diameter) as well as particles present on the disc surfaces possibly related to the high initial dissolution rates. Material swelling or precipitation was observed for discs containing 10.6 or 15.8% (w/w) SDS. UV imaging revealed increased griseofulvin concentrations near the solid-liquid interface of griseofulvin-SDS discs, e.g., a 45- fold increase in concentration was observed for discs containing 10.6% (w/w) SDS as compared to discs without SDS, which is the likely cause of the enhanced dissolution rates found for the co-compressed griseofulvin-SDS discs. © 2017 Elsevier B.V. All rights reserved. 1. Introduction Surfactants, such as sodium dodecyl sulfate (SDS), are used in tablets to increase the bioavailability of poorly soluble drugs [1]. FDA's inactive ingredients database has 54 approved drug products containing SDS, with loads as high as 96 mg per tablet or capsule [2]. The function of surfactants in tablets is to facilitate dissolution since the dose can rarely be solubilized entirely by the amount of surfactant in a tablet [3e6]. Upon tablet disintegration and sur- factant dissolution, the solubility of the drug in the intestinal fluid is only increased to a minor degree by the inclusion of surfactants [3e6]. Surfactants have previously been reported to produce a faster disintegration of the tablet and dispersion of smaller drug particles, which results in a higher dissolution rate that may lead to improved bioavailability [3,4]. The dissolution of griseofulvin and felodipine from drug-SDS discs has been studied using a miniaturized rotating disc setup [7]. The drug dissolution rate was observed to increase several or- ders of magnitude when 30% (w/w) SDS was present in the discs as compared to discs without SDS. The pronounced effect of SDS on drug dissolution rate was not caused by 1) an increased surface area as SDS dissolved from the discs; 2) increased solubility of the drug due to the surfactants in the bulk medium; nor 3) changes in solid state properties of the drug by co-compression with SDS. It was suggested that a high local concentration of SDS near the solid- liquid interface would increase drug solubility locally. The improved local solubility would provide a steeper concentration gradient resulting in faster dissolution [7]. UV imaging, also termed dissolution imaging, has been intro- duced as a method for studying various drug dissolution and release processes [8e17]. UV imaging allows 2D concentration * Corresponding author. Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. E-mail addresses: peter.madelung@sund.ku.dk (P. Madelung), Poul.Bertelsen@ takeda.com (P. Bertelsen), jette.jacobsen@sund.ku.dk (J. Jacobsen), anette. mullertz@sund.ku.dk (A. Müllertz), jesper.ostergaard@sund.ku.dk (J. Østergaard). Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst http://dx.doi.org/10.1016/j.jddst.2017.05.010 1773-2247/© 2017 Elsevier B.V. All rights reserved. Journal of Drug Delivery Science and Technology 39 (2017) 516e522