Versatility on demand - The case for semi-solid micro-extrusion in pharmaceutics.

Since additive manufacturing of pharmaceuticals has been introduced as viable method to produce individualized drug delivery systems with complex geometries and release profiles, semi-solid micro-extrusion has shown to be uniquely beneficial. Easy incorporation of actives, room-temperature processability and avoidance of cross-contamination by using disposables are some of the advantages that led many researchers to focus their work on this technology in the last few years. First acceptability and in-vivo studies have brought it closer towards implementation in decentralized settings. This review covers recently established process models in light of viscosity and printability discussions to help develop high quality printed medicines. Quality defining formulation and process parameters to characterize the various developed dosage forms are presented before critically discussing the role of semi-solid micro-extrusion in the future of personalized drug delivery systems. Remaining challenges regarding regulatory guidance and quality assurance that pose the last hurdle for large scale and commercial manufacturing are addressed.

3D-Printing with precise layer-wise dose adjustments for paediatric use via pressure-assisted microsyringe printing.

The establishment of 3D-printing as manufacturing process for oral solid dosage forms enables new options for the individualized medicine. The aim of this work was to develop a novel drug-printing model using pressure-assisted microsyringe (PAM) technology, which allows the precise dispensing of drug substances. Printed tablets with different numbers of layers, mimicking different doses for pediatric subgroups, were analyzed regarding mass variation, friability, thickness and disintegration time. Furthermore, the uniformity of dosage units and the dissolution behavior were investigated. Friability was <0.3% in all cases, which demonstrates the ability of PAM printing to manufacture robust solid dosage. Disintegration results showed the dependency of the disintegration on the number of layers and therefore on the compact mass of polymer. However, all tablets disintegrated within 3 min and fulfilled the requirements of immediate release tablets of the USP and orodispersible tablets according to the Ph. Eur. Results of uniformity dosage units confirmed the successful manufacturing of the intended individualized doses. Drug dissolution appeared to be dependent on the number of layers. An increase of layers resulted in a decrease of the drug release rate. Further, the drug release could be correlated to the surface area/volume (SA/V) ratio.