Boisen, Anja

Keller, Stephan Sylvest

Marizza, Paolo

Müllertz, A.

Nagstrup, Johan

Nielsen, L. Hagner

Petersen, Ritika Singh

Online Research Database In Technology

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Hagner; Marizza, Paolo; Petersen, Ritika Singh; Nagstrup, Johan;Müllertz, A.; Boisen, AnjaPublished in:Proceedings of the 10th International Conference and Workshop on Biological BarriersPublication date:2014Link back to DTU OrbitCitation (APA):Keller, S. S., Nielsen, L. H., Marizza, P., Petersen, R. S., Nagstrup, J., Müllertz, A., & Boisen, A. (2014).Microfabricated containers for pH-triggered drug release in the upper intestine. In Proceedings of the 10thInternational Conference and Workshop on Biological BarriersPlease create your abstract using the following template and send this word document to biobarriers2014@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 ‘doc’ file (Author A B.doc).  Microfabricated containers for pH-triggered drug release in the upper intestine  Sylvest Keller S.11Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark ; Hagner Nielsen L.2; Marizza P. 1, Singh R. 1, Nagstrup J. 1, Müllertz A.2; Boisen A.1 2Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark  In the past years, microfabricated containers were introduced as new concept for oral drug delivery [1,2]. The microcontainers provide a cavity that is filled with drug formulation and sealed with a polymer membrane. In this way degradation of the drug in the stomach is prevented and the drug release is triggered by dissolution or degradation of the membrane in the intestine. Here, we present our recent advances in the development of microcontainers for oral drug delivery, with particular focus on new methods for drug loading and integration of enteric coatings. Prototype microcontainers with inner diameters of 230 µm were fabricated using epoxy resins (SU-8, Microchem, USA) patterned by UV exposure (Fig. 1a). Alternatively, biodegradable containers were prepared. In this case hot embossing in biodegradable polymers such as Poly(lactic acid) (PLLA) was used to define the bottom and the walls of the cavities (Fig. 1b). The microcontainers were filled with drug using two different methods: a) Loading of drug powder and b) deposition of Poly(vinylpyrrolidone) (PVP) in the cavities by inkjet printing followed by supercritical drug impregnation (Fig. 2) [3]. Finally, a lid of enteric polymer (Eudragit L100, Evonik Industries, Germany) sealing the open side of the cavity was selectively deposited on the microcontainer using spray coating through a shadow mask (Fig.3) [4]. Fig.4 shows in vitro drug release from microcontainers loaded with ketoprofen by supercritical impregnation. Furthermore, pH-triggered release was demonstrated by in vitro experiments with microcontainers filled with solid dispersions of furosemide and cinnarizine and coated with Eudragit L100.                                                                                            Figure 1: Microcontainers fabricated by a) UV patterning of  Figure 2: Drug loading combining a) inkjet printing and b) drug SU-8 and b) hot embossing in PLLA  impregnation in supercritical CO2         Figure 3: Microcontainers filled with drug powder  Figure 4: In vitro release profiles for 625 microcontainers filled with PVP and loaded a) before and b) after deposition of Eudragit L100  with ketoprofen by supercritical impregnation                                                                                                                        The authors would like to acknowledge NAnoMEChanical sensors and actuators, fundamentals and new directions (NAMEC) – a VKR Centre of Excellence and Villum Kann Rasmussen Foundation for the financial support.   References: 1. Ahmed, A., Bonner, C., Desai, T.A.: J Control Release. 2002, 81: 291-306.  2. Chirra, H.D., Desai T.A.: Adv Drug Deliv Rev. 2012, 64: 1569-78.  3. Marizza, P. et al.: J. Control. Release. 2014, 173:1-9. 4. Keller, S., Bosco, F.G., Boisen, A.: Microelec. Eng. 2013, 110:427-431. 100 µm 50 µmscCO2+drug100 µma) b)100 µm01020304050607080901000 1 2 3 4 5 6 7 8 9 10200 bar 40°C 4 h200 bar 40°C 1 h100 bar 40°C 4 h100 bar 40°C 1 hEmpty containers 200bar 40°C 4hReleasedketoprofen(µg/ml)time (hours)

Microfabricated containers for pH-triggered drug release in the upper intestine

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Microfabricated containers for pH-triggered drug release in the upper intestine

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