Loading of microcontainers for oral drug delivery

Paolo Marizza

    Research output: Book/ReportPh.D. thesis

    1126 Downloads (Pure)


    The pharmaceutical research is facing several obstacles in the development of drug products for the oral delivery. The main problem deals with the intrinsic chemical nature of the new drug candidates, which are often poorly soluble and barely absorbed in the gastro-intestinal tract. Furthermore, they are usually degraded before they are absorbed. These combined factors considerably reduce the bioavailability of many active ingredients. Several strategies have been developed to overcome these challenges. One of them are microfabricated drug delivery devices. Microreservoir based-systems are characterized by small dimensions (100-500 μm), mucoadhesive properties, asymmetric geometry and unidirectional drug release. In the fabrication of these microcontainers, an important task is the drug loading. The state of the art in this field is based on traditional methods used in microtechnology, which for this application in most cases are cost ineffective and unsuitable for large scale production.
    The goal of this project was to develop novel techniques for loading of poorly soluble drugs and macromolecules in microcontainers. The research focused on simple and cost effective methods, suitable for a large group of drugs and with the perspective of mass production.
    In a first instance, the suitability of inkjet printing as filling method was elucidated. Solutions containing furosemide and lipid based formulations of insulin were dispensed into microcontainers. Secondly, this technique was successfully utilized for the deposition of polymer matrices in microcontainers, which afterwards were loaded with the drug. For this purpose, inkjet printing of solutions of poly(vinylpyrrolidone) was developed. The polymer deposition was homogeneous and reproducible, which demonstrated that inkjet printing is a valuable technology to dispense controlled amounts of polymer into microcontainers. Subsequently, polymer filled-containers were loaded with drug. To achieve this, supercritical impregnation technology was successfully employed. Furthermore, in vitro drug dissolution studies showed that the loading yields and the release properties of the microdevices can be tuned. The effect of different impregnation process parameters on the loading yields was studied, and the drugpolymer interactions were characterized with various spectroscopic techniques. This technique allowed loading of large arrays of the microcontainers in one single operation with high accuracy and repeatability. Furthermore, the combination of inkjet printing and supercritical impregnation allows to minimize the waste of possibly expensive active ingredients.
    A successful process for the definition of micropatterns of poly(vinylpyrrolidone) hydrogel by means of UV photolithography was developed. The fabrication of polymer patterns was optimized and loading with both small hydrophobic drugs and proteins was demonstrated. Finally, structural properties of hydrogels were elucidated by rheology and NMR with the perspective of controlling the drug release.
    The loading techniques developed in this thesis represent a novelty in the field of microfabricated drug delivery devices. The methods utilized in this research work are potentially integrated in the fabrication process of biopolymer microcontainers.
    Original languageEnglish
    PublisherTechnical University of Denmark
    Number of pages155
    Publication statusPublished - 2014

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