Boisen, Anja

Keller, Stephan Sylvest

Marizza, Paolo

Melero, A.

Müllertz, A.

Nielsen, Line Hagner

Petersen, Ritika Singh

Rades, T.

In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion and oral bioavailability. SU-8 microcontainers were fabricated using lithography resulting in microcontainers with an inner diameter of 220 μm. The PLLA microcontainers were prepared by hot embossing with inner diameter of 240 μm (Figure 1). In terms of drug filling, the SU-8 microcontainers were filled with polyvinylpyrrolidone (PVP) by inkjet printing followed by supercritical CO2 impregnation of ketoprofen into the PVP matrix. As an alternative filling method, the powder of amorphous sodium salt of furosemide, (ASSF) was filled into the SU-8 microcontainers. The PLLA microcontainers were filled with drug formulation by embossing the microcontainers into a polycaprolactone (PCL) and furosemide (4:1 w/w) layer. For the ASSF-filled microcontainers, an enteric-resistant lid of Eudragit L100 was spray coated onto the cavity of the microcontainers. From coated ASSF-filled microcontainers, a fast release in simulated intestinal medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate constant of ASSF was 1.5 fold higher, when ASSF was confined in the microcontainers compared to a furosemide solution. Micrographs of the small intestine after the perfusion showed that the microcontainers were engulfed by the intestinal mucus. For the in vivo studies, the rats were dosed orally with capsules containing ASSF-filled microcontainers coated with Eudragit L100. As control, capsules were filled with the powder of ASSF and the capsules were coated with Eudragit L100. The oral bioavailability study showed that the relative oral bioavailability of ASSF in microcontainers is 220±43% when compared to drug-filled capsules coated with Eudragi

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Downloaded from orbit.dtu.dk on: Nov 09, 2017Microcontainers - an oral drug delivery system for poorly soluble drugsNielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo; Keller, Stephan Sylvest; Melero, A.; Rades,T.; Müllertz, A.; Boisen, AnjaPublication date:2016Document VersionPublisher's PDF, also known as Version of recordLink back to DTU OrbitCitation (APA):Nielsen, L. H., Petersen, R. S., Marizza, P., Keller, S. S., Melero, A., Rades, T., ... Boisen, A. (2016).Microcontainers - an oral drug delivery system for poorly soluble drugs. Poster session presented at BioBarriers2016, Saarbrücken, Germany.Please create your abstract using the following template and send the document as pdf-file to  Biobarriers2016@mx.uni-saarland.de Please do not modify the format of this template! Abstract limit is 1 page A4.  NOTE: Please save your abstract file according to the name of the presenting author as a ‘pdf ’ file (Author A B.pdf).   Microcontainers - an oral drug delivery system for poorly soluble drugs  Hagner Nielsen L.1, Petersen R.S.1, Marizza P1., Keller S.S.1, Melero A.2, Rades T.3, Müllertz A.3,Boisen A.1  1Department of Micro and Nanotechnology, Technical University of Denmark, Kgs. Lyngby, Denmark  2Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain 3Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark  In oral delivery, it can sometimes be necessary to employ drug delivery systems to achieve targeted delivery to the intestine. Microcontainers are polymeric, cylindrical devices in the micrometer size range (Figure 1), and are suggested as a promising oral drug delivery system [1],[2]. The purpose of these studies was to fabricate microcontainers in either SU-8 or biodegradable poly-L-lactic acid (PLLA), and fill the microcontainers with poorly soluble drugs. Furthermore, the application of the microcontainers as an oral drug delivery system was investigated in terms of release, in situ intestinal perfusion and oral bioavailability.  SU-8 microcontainers were fabricated using lithography resulting in microcontainers with an inner diameter of 220 µm. The PLLA microcontainers were prepared by hot embossing with inner diameter of 240 µm (Figure 1). In terms of drug filling, the SU-8 microcontainers were filled with polyvinylpyrrolidone (PVP) by inkjet printing followed by supercritical CO2 impregnation of ketoprofen into the PVP matrix. As an alternative filling method, the powder of amorphous sodium salt of furosemide, (ASSF) was filled into the SU-8 microcontainers. The PLLA microcontainers were filled with drug formulation by embossing the microcontainers into a polycaprolactone (PCL) and furosemide (4:1 w/w) layer. For the ASSF-filled microcontainers, an enteric-resistant lid of Eudragit L100 was spray coated onto the cavity of the microcontainers. From coated ASSF-filled microcontainers, a fast release in simulated intestinal medium at pH 6.5 was observed. In situ intestinal perfusions were performed in rats of the Eudragit-coated ASSF-filled microcontainers and compared to a furosemide solution. At the end of the study, the small intestine was harvested from the rat and imaged under a light microscope. The absorption rate constant of ASSF was 1.5 fold higher, when ASSF was confined in the microcontainers compared to a furosemide solution. Micrographs of the small intestine after the perfusion showed that the microcontainers were engulfed by the intestinal mucus. For the in vivo studies, the rats were dosed orally with capsules containing ASSF-filled microcontainers coated with Eudragit L100. As control, capsules were filled with the powder of ASSF and the capsules were coated with Eudragit L100. The oral bioavailability study showed that the relative oral bioavailability of ASSF in microcontainers is 220±43% when compared to drug-filled capsules coated with Eudragit (Figure 2).     Acknowledgments: The authors would like to acknowledge the Danish Research Council for Technology and Production (FTP), Project DFF - 4004-00120B for financial support. Moreover, the Danish National Research Foundation, project: DNRD122 is acknowledged. References: 1. Chirra, HD. et. al.: Adv. Healthc. Mater. 2014, 3: 1648–1654. 2. Nielsen, LH. et al.: Eur J Pharm and Biopharm. 2012, 81: 418-25.  

Microcontainers - an oral drug delivery system for poorly soluble drugs

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Microcontainers - an oral drug delivery system for poorly soluble drugs

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