Journal of Pharmaceutical and Biomedical Analysis 83 (2013) 49–56 Contents lists available at SciVerse ScienceDirect Journal of Pharmaceutical and Biomedical Analysis jou rn al hom e page: www.elsevier.com/locate/jpba Real-time in vitro dissolution of 5-aminosalicylic acid from single ethyl cellulose coated extrudates studied by UV imaging Mette Høg Gaunø a,b,1 , Thomas Vilhelmsen c , Crilles Casper Larsen d , Johan Peter Boetker a , Jørgen Wittendorff b , Jukka Rantanen a , Jesper Østergaard a,∗ a Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark b Pharmaceutical Drug Development, International PharmaScience Center, Ferring Pharmaceuticals A/S, Kay Fiskers Plads 11, DK-2300 Copenhagen S, Denmark c Oral Product and Process Development, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark d Process Development & Pilot Plant, Ferring International Center SA, Ch. de la Vergognausaz 50, 1162 St-Prex, Switzerland a r t i c l e i n f o Article history: Received 24 January 2013 Received in revised form 12 April 2013 Accepted 15 April 2013 Available online 27 April 2013 Keywords: 5-Aminosalicylic acid Coating defects Dissolution Functional coating Real-time drug dissolution UV imaging a b s t r a c t The purpose of this study was to investigate the in vitro release of 5-aminosalicylic acid from single extrudates by UV imaging and to explore the technique as a visualization tool for detecting film coating defects on extrudates coated with a thin ethyl cellulose layer. 5-Aminosalicylic acid extrudates were film coated with ethyl cellulose in a typical lab system coater equipped with one Wurster partition. Dissolution testing was performed first in a conventional paddle dissolution apparatus and second, in a flow through geometry equipped with a UV imaging system. Selected film coated extrudates from four different coating levels were placed in agarose gels and UV imaging was performed for a total of 240 min. Absorbance maps were obtained thus visualizing the release of 5-aminosalicylic acid over time and it was possible to detect a decrease in release as a function of increased ethyl cellulose coating weight gain. Using a calibration curve the released amount was calculated and the individual release profiles for each coating weight gain in general resulted in comparable release profiles. Furthermore, the release profiles were consistent with the dissolution results obtained from the paddle dissolution testing. The release from defect extrudates was visualized by the absorbance maps and the release was highest from the compromised part of the extrudates. UV imaging has proven to be a useful technique to visualize the release of 5-aminosalicylic acid from single film coated extrudates and it has potential for detection of film coating defects. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Film coating is widely applied in the pharmaceutical industry as a means to obtain a desired functionality of dosage forms, including taste masking, appearance, or controlled release of the active com- pound [1,2]. In terms of controlled release, film coating is applied to achieve predefined drug release profiles. Most often the polymer is transferred to the particulate drug containing core from a suit- able solution or dispersion using spray atomization processes. The film properties are influenced by a number of formulation [3–5], equipment [6–8], and process parameters [7,9,10]. ∗ Corresponding author at: Department of Pharmacy, Faculty of Health and Medi- cal Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen Ø, Denmark. Tel.: +45 35 33 65 85; fax: +45 35 33 60 30. E-mail address: jesper.ostergaard@sund.ku.dk (J. Østergaard). 1 Present address: Oral Product and Process Development, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark. In order to obtain a dosage form with the desired release char- acteristics, thorough knowledge and control of the coating process is required. However, it is also essential that the quality of the coat- ing is not compromised in the subsequent production and handling processes, e.g. due to mechanical damage. The density and thick- ness of the coating on tablets, pellets, and granules have been characterized using NIR spectroscopy [11], Raman spectroscopy [12], and in combination with different imaging techniques such as terahertz pulsed imaging [13,14]. Especially the surface struc- ture has been characterized by different imaging techniques [15] and investigation of coating defects by e.g. confocal laser scan- ning microscopy [16]. However, these techniques are often time consuming and provide often only structural information on a molecular level, whereas the impact of the surface structure on the coating performance is commonly lacking. Dissolution testing remains the most widely used approach for assessing product per- formance and quality attributes of tablets and multi-particulate film coated dosage forms. Conventional dissolution testing is often performed according to the paddle method as described in Phar- macopoeias, where the dosage form is placed in a suitable buffer 0731-7085/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jpba.2013.04.028