Boisen, Anja

Keller, Stephan Sylvest

Marizza, Paolo

Rades, T.

Online Research Database In Technology

                       General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.  • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal   If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.     Downloaded from orbit.dtu.dk on: Dec 20, 2017Inkjet printing as a novel drug loading technique of micro-containersMarizza, Paolo; Keller, Stephan Sylvest; Rades, T.; Boisen, AnjaPublished in:Proceedings of the 6th Annual PSSRC Symposium 2012Publication date:2012Link back to DTU OrbitCitation (APA):Marizza, P., Keller, S. S., Rades, T., & Boisen, A. (2012). Inkjet printing as a novel drug loading technique ofmicro-containers. In Proceedings of the 6th Annual PSSRC Symposium 20126th Annual Symposium Inkjet printing as a novel drug loading technique of micro-containers  P. Marizza, S. Sylvest Keller, T. Rades, A. Boisen   Department of Micro- and Nanotechnology, Technical University of Denmark, Kgs Lyngby 2800, Denmark    Purpose We present an innovative technique to dispense precise amounts of drug solutions into large arrays of microscopic wells as an oral drug delivery device.   Introduction Micro-containers are designed as a confinement of micro-doses of active ingredient to be delivered through the oral route [1]. Drugs of interest are those with a low solubility in the intestinal fluid, and those fragile molecules that need a protection against low pH and enzymatic degradation. Furosemide as been chosen as a test drug with a poor solubililty in water.  Ink-jet printing is a recent technology commonly used in the field of biosensing and polymer processing [2]. In this work it has been used to prepare micro doses of active pharmaceutical ingredient for the oral administration.   Materials and Methods Micro-containers are fabricated with a cylindrical shape with an photoresist with two steps of negative photo-lithography. Cavity diameters go from 300 µm down to 50 µm. A SEM picture of a micro-well can be seen in figure 1. A nano-plotter (NP 2.1, GeSim), designed to spot micro-arrays of water-based solutions, has been used to dispense in pico-liter quantities a solution of 5 mg/ml of furosemide in an ethanol-DMSO mixture of (50/50) into micro-containers cylindrical cavities.    Fig. 1: Microcontainers of 300 µm in diameter Fig., 2: Top view of an array of micro wells filled with dried furosemide solution   PSSRC – Pharmaceutical Solid State Research Cluster 1  6th Annual Symposium  Results and discussion  Ink-jet printing has been shown to be a suitable technique to dispense defined volume of solution in a high reproducible way [3], which is a crucial parameter in order to control, for instance, the dose in a pharmaceutical product. The alignment of pipette and micro-containers is performed with a microscope either manually or with a structure recognition program. The pipette head can be programmed to spot large arrays and complex patterns. Regularity in the spatial distribution of spots has been optimized by tuning spotting parameters (voltage, pulse-width and frequency of the signal applied to piezo-pipette).  Dispensable volume goes from 0.3 to 2 nanoliters and by means of stroboscope imaging, droplet volume and shape can be tuned. The solution is soaked in and spurted out by means of a pneumatic system using water as mean. Furosemide solution can be dispensed with high precision into arrays of micro-wells (see figure 2) with different parameters. The content of the drug can be controlled varying its original concentration in the solutions and the number of dispensed droplets.   Conclusions In conclusion, we demonstrate a very versatile filling technique for 3D micro-structures that can be tuned for several purposes, including promising applications in the field of micro-devices for drug delivery and biomedical research.   Future Work  The solid state of the drug has to be investigated by means of Raman spectroscopy and X- ray diffraction. A further step of this loading technique, is the application to other drugs, like protein and other fragile active compound.    [1] K.M. Ainslie, C. M. Kraning, T. A. Desai, Lab on a Chip 8 (2008) 1042-1047. [2] B.J. de Gans, P. C. Duineveld, U. S. Schubert, Advanced Materials 16 (2004) 203-213.  [3] I. Barbulovic-Nad, M. Lucente, Y. Sun, M. Zhang, A. R. Wheeler, M. Bussmann 26 (2006) No. 4, 237-259     PSSRC – Pharmaceutical Solid State Research Cluster 2  

Inkjet printing as a novel drug loading technique of micro-containers

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Inkjet printing as a novel drug loading technique of micro-containers

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