1 Department of Micro- and Nanotechnology, Technical University of Denmark2 Nanoprobes, Department of Micro- and Nanotechnology, Technical University of Denmark3 Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics, Center, Technical University of Denmark
The pharmaceutical industry is presently facing several obstacles in developing oral drug delivery systems. This is primarily due to the nature of the discovered drug candidates. The discovered drugs often have poor solubility and low permeability across the gastro intestinal epithelium. Furthermore, they are often degraded before they can be absorbed. The result is low bioavailability of the drugs. To overcome these challenges, better drug delivery systems need to be developed. Recently, micro systems have emerged as promising candidates to solve the challenges of poor solubility, low permeability and degradation. These systems are for the majority based on traditional materials used in micro technology, such as SU-8, silicon, poly(methyl methacrylate). The next step in developing these new drug delivery systems is to replace classical micro fabrication materials with biodegradable polymers. In order to successfully do this, methods for fabricating micro structures in biodegradable polymers need to be developed. The goal of this project has been to develop methods for micro fabrication in biodegradable polymers and to use these methods to produce micro systems for oral drug delivery. This has successfully been achieved by fabrication of micro container systems made of poly(Llactic acid) and polycaprolactone. To achieve this, polymer solutions have been developed using the theory of Hansen’s solubility parameters. The solutions are used to fabricate polymer films by spin coating, which are used in the fabrication of micro devices for oral drug delivery. Films consisting of both polymer and pharmaceuticals have also been developed by spin coating. A deep reactive ion etch producing sloped sidewalls for stamp production has been developed. The sloped sidewalls ensure a successful separation of stamp and film after patterning. Large scale methods for filling of micro reservoirs based on embossing, screen printing and solvent casting have been developed. In vitro drug release experiments on both type of micro devices have been performed. The experiments show that most of the drug is released from the developed devices. Additionally, it has been shown that it is possible to control the release of drug by adding polymeric coatings.