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Abstract3d printing is capable of providing dose individualization for pediatric medicines and translating the precision medicine approach into practical application. In pediatrics, dose individualization and preparation of small dosage forms is a requirement for successful therapy, which is frequently not possible due to the lack of suitable dosage forms. For precision medicine, individual characteristics of patients are considered for the selection of the best possible API in the most suitable dose with the most effective release profile to improve therapeutic outcome. 3d printing is inherently suitable for manufacturing of individualized medicines with varying dosages, sizes, release profiles and drug combinations in small batch sizes, which cannot be manufactured with traditional technologies. However, understanding of critical quality attributes and process parameters still needs to be significantly improved for this new technology. To ensure health and safety of patients, cleaning and process validation needs to be established. Additionally, adequate analytical methods for the in-process control of intermediates, regarding their printability as well as control of the final 3d printed tablets considering any risk of this new technology will be required. The PolyPrint consortium is actively working on developing novel polymers for fused deposition modeling (FDM) 3d printing, filament formulation and manufacturing development as well as optimization of the printing process, and the design of a GMP-capable FDM 3d printer. In this manuscript, the consortium shares its views on quality aspects and measures for 3d printing from drug-loaded filaments, including formulation development, the printing process, and the printed dosage forms. Additionally, engineering approaches for quality assurance during the printing process and for the final dosage form will be presented together with considerations for a GMP-capable printer design.

The transport of drugs across the blood-brain barrier is challenging. The use of peptide sequences derived from viruses with a central nervous system (CNS) tropism is one elegant option. A prominent example is the rabies virus glycopeptide-29 (RVG-29), which is said to enable a targeted brain delivery. Although the entry mechanism of the rabies virus into the CNS is very well characterized, it is unknown whether RVG-29-functionalized drug delivery systems (DDSs) follow this pathway. RVG-29-functionalized DDSs present themselves with modifications of the RVG-29 peptide sequence and different physicochemical properties compared to the rabies virus. To our surprise, the impact of these changes on the functionality is completely neglected. This review explores virus-related CNS-targeting strategies by comparing RVG-29-functionalized DDSs with regard to their peptide modification, physiochemical properties and their behavior in cell culture studies with a special focus on the original pathway of rabies virus entry into the CNS.

A noninvasive, sensitive and reproducible method is presented to assess nanocrystal dissolution. In situ measurements based on light scattering allow a straightforward experimental setup with high temporal resolution.

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The aim of this research was the production of low-dosed filaments via hot-melt extrusion (HME) with the model drug pramipexole for the treatment of Parkinson’s disease. The active pharmaceutical ingredient (API) and one of the polymers polyvinyl alcohol (PVA) or basic butylated methacrylate copolymer (bPMMA) were fed by various dosing techniques with the aim of achieving the smallest deviation (RSD) from the target concentration of 0.1% (w/w) pramipexole. It was found that deviation from target pramipexole concentration occurred due to degradation products in bPMMA formulations. Additionally, material temperature above 120 °C led to the formation of the anhydrous form of pramipexole within the extruded filaments and need to be considered in the calculation of the recovered API. This study clearly shows that even if equilibrium state of the extrusion parameters was reached, equilibrium condition for drug content was reached relatively late in the process. In addition, the RSD calculated by the Stange–Poole equation was proposed by us to predict the final content uniformity considering the sample size of the analyzed filament. The calculated RSD, depending on sample size and drug load, can serve as upper and lower limits of variation from target concentration and can be used to evaluate the deviations of drug content in equilibrium conditions of the HME process. The lowest deviations from target concentration in equilibrium condition for drug content were obtained in filaments extruded from previously prepared granule mixtures (RSD = 6.00%, acceptance value = 12.2). These promising results can be transferred to other API–excipient combinations to produce low-dosed filaments, which can be used for, e.g., fused filament 3D printing. The introduced calculation of the RSD by Stange–Poole equation can be used for precise determination of the homogeneity of an extruded batch.

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