Evaluation of Printability of PVA-Based Tablets from Powder and Assessment of Critical Rheological Parameters.

Fused deposition modeling (FDM) is a rather new technology in the production of personalized dosage forms. The melting and printing of polymer-active pharmaceutical ingredient (API)-mixtures can be used to produce oral dosage forms with different dosage as well as release behavior. This process is utilized to increase the bioavailability of pharmaceutically relevant active ingredients that are poorly soluble in physiological medium by transforming them into solid amorphous dispersions (ASD). The release from such ASDs is expected to be faster and higher compared to the raw materials and thus enhance bioavailability. Printing directly from powder while forming ASDs from loperamide in Polyvinylalcohol was realized. Different techniques such as a change in infill and the incorporation of sorbitol as a plastisizer to change release patterns as well as a non-destructive way for the determination of API distribution were shown. By measuring the melt viscosities of the mixtures printed, a rheological model for the printer used is proposed.

Phase homogeneity in ternary amorphous solid dispersions and its impact on solubility, dissolution and supersaturation - Influence of processing and hydroxypropyl cellulose grade.

As performance of ternary amorphous solid dispersions (ASDs) depends on the solid-state characteristics and polymer mixing, a comprehensive understanding of synergistic interactions between the polymers in regard of dissolution enhancement of poorly soluble drugs and subsequent supersaturation stabilization is necessary. By choosing hot-melt extrusion (HME) and vacuum compression molding (VCM) as preparation techniques, we manipulated the phase behavior of ternary efavirenz (EFV) ASDs, comprising of either hydroxypropyl cellulose (HPC)-SSL or HPC-UL in combination with Eudragit® L 100-55 (EL 100-55) (50:50 polymer ratio), leading to single-phased (HME) and heterogeneous ASDs (VCM). Due to higher kinetic solid-state solubility of EFV in HPC polymers compared to EL 100-55, we visualized higher drug distribution into HPC-rich phases of the phase-separated ternary VCM ASDs via confocal Raman microscopy. Additionally, we observed differences in the extent of phase-separation in dependence on the selected HPC grade. As HPC-UL exhibited decisive lower melt viscosity than HPC-SSL, formation of partially miscible phases between HPC-UL and EL 100-55 was facilitated. Consequently, as homogeneously mixed polymer phases were required for optimal extent of solubility improvement, the manufacturing-dependent differences in dissolution performances were smaller using HPC-UL, instead of HPC-SSL, i.e. using HPC-UL was less demanding on shear stress provided by the process.