Microcontainers - an oral drug delivery system for poorly soluble drugs

Line Hagner Nielsen, Ritika Singh Petersen, Paolo Marizza, Stephan Sylvest Keller, A. Melero, T. Rades, A. Müllertz, Anja Boisen

Research output: Contribution to conferencePosterResearchpeer-review

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Abstract

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
Original languageEnglish
Publication date2016
Number of pages1
Publication statusPublished - 2016
EventBioBarriers 2016: 11th Conference and Workshop on Biological Barriers - Universität des Saarlandes, Saarbrücken, Germany
Duration: 7 Mar 20169 Mar 2016

Conference

ConferenceBioBarriers 2016
LocationUniversität des Saarlandes
CountryGermany
CitySaarbrücken
Period07/03/201609/03/2016

Bibliographical note

Poster at Conference, BioBarriers 2016, Saarbrücken, Germany, March 2016

Cite this

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 BioBarriers 2016, Saarbrücken, Germany.
Nielsen, Line Hagner ; Petersen, Ritika Singh ; Marizza, Paolo ; Keller, Stephan Sylvest ; Melero, A. ; Rades, T. ; Müllertz, A. ; Boisen, Anja. / Microcontainers - an oral drug delivery system for poorly soluble drugs. Poster session presented at BioBarriers 2016, Saarbrücken, Germany.1 p.
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title = "Microcontainers - an oral drug delivery system for poorly soluble drugs",
abstract = "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",
author = "Nielsen, {Line Hagner} and Petersen, {Ritika Singh} and Paolo Marizza and Keller, {Stephan Sylvest} and A. Melero and T. Rades and A. M{\"u}llertz and Anja Boisen",
note = "Poster at Conference, BioBarriers 2016, Saarbr{\"u}cken, Germany, March 2016; BioBarriers 2016 : 11th Conference and Workshop on Biological Barriers ; Conference date: 07-03-2016 Through 09-03-2016",
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Nielsen, LH, Petersen, RS, Marizza, P, Keller, SS, Melero, A, Rades, T, Müllertz, A & Boisen, A 2016, 'Microcontainers - an oral drug delivery system for poorly soluble drugs' BioBarriers 2016, Saarbrücken, Germany, 07/03/2016 - 09/03/2016, .

Microcontainers - an oral drug delivery system for poorly soluble drugs. / Nielsen, Line Hagner; Petersen, Ritika Singh; Marizza, Paolo; Keller, Stephan Sylvest; Melero, A.; Rades, T.; Müllertz, A.; Boisen, Anja.

2016. Poster session presented at BioBarriers 2016, Saarbrücken, Germany.

Research output: Contribution to conferencePosterResearchpeer-review

TY - CONF

T1 - Microcontainers - an oral drug delivery system for poorly soluble drugs

AU - Nielsen, Line Hagner

AU - Petersen, Ritika Singh

AU - Marizza, Paolo

AU - Keller, Stephan Sylvest

AU - Melero, A.

AU - Rades, T.

AU - Müllertz, A.

AU - Boisen, Anja

N1 - Poster at Conference, BioBarriers 2016, Saarbrücken, Germany, March 2016

PY - 2016

Y1 - 2016

N2 - 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

AB - 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

M3 - Poster

ER -

Nielsen LH, Petersen RS, Marizza P, Keller SS, Melero A, Rades T et al. Microcontainers - an oral drug delivery system for poorly soluble drugs. 2016. Poster session presented at BioBarriers 2016, Saarbrücken, Germany.