Assessment of Tribo-charging and Continuous Feeding Performance of Direct Compression Grades of Isomalt and Mannitol Powders.

Tribo-charging is often a root cause of mass flow deviations and powder adhesion during continuous feeding. Thus, it may critically impact product quality. In this study, we characterized the volumetric (split- and pre-blend) feeding behavior and process-induced charge of two direct compression grades of polyols, galenIQ™ 721 (G721) for isomalt and PEARLITOL® 200SD (P200SD) for mannitol, under different processing conditions. The feeding mass flow range and variability, hopper end fill level, and powder adhesion were profiled. The feeding-induced tribo-charging was measured using a Faraday cup. Both materials were comprehensively characterized for relevant powder properties, and their tribo-charging was investigated for its dependence on particle size and relative humidity. During split-feeding experiments, G721 showed a comparable feeding performance to P200SD with lower tribo-charging and adhesion to the screw outlet of the feeder. Depending on the processing condition, the charge density of G721 ranged from -0.01 up to -0.39 nC/g, and for P200SD from -3.19 up to -5.99 nC/g. Rather than differences in the particle size distribution of the two materials, their distinct surface and structural characteristics were found as the main factors affecting their tribo-charging. The good feeding performance of both polyol grades was also maintained during pre-blend feeding, where reduced tribo-charging and adhesion propensity was observed for P200SD (decreasing from -5.27 to -0.17 nC/g under the same feeding settings). Here, it is proposed that the mitigation of tribo-charging occurs due to a particle size-driven mechanism.

Predicting powder feedability: A workflow for assessing the risk of flow stagnation and defining the operating space for different powder-feeder combinations.

Powder feeding is of critical importance for continuous manufacturing (CM) since next to in-process segregation it is the phenomenon primarily responsible for fluctuations in content uniformity and for content deviations in the final drug product. So far, feeding studies have focused on the characterization of specific feeders and the prediction of their performance for various materials. This work presents a more holistic approach, an early general assessment of the "feedability" of raw materials. With that regard, we established a workflow to: i) predict potential feeding issues, such as the flow stagnation in the hopper based on both the material attributes and the feeder's geometry; and ii) predict the feed rate space using various feeder/screw combinations for powders with an acceptable risk of hopper flow stagnation. Statistical models were developed for this twofold approach using a dataset comprising nine powders and four different feeders. In order to include different feeding equipment into the statistical models, novel equipment descriptors (capturing the effect of different geometries) and performance indicators (the end fill level as indicator for the risk of powder flow stagnation) were introduced. The application of the workflow was demonstrated for a simple formulation, and model validation was successfully performed for an additional powder that was not contained in the original dataset. Finally, the most relevant material attributes were identified, and reduced material characterization data sets were investigated in terms of effects on the model's prediction performance. The workflow presents a promising tool for initial process assessment in early-phase development.

Insights into the Impact of Nanostructural Properties on Powder Tribocharging: The Case of Milled Salbutamol Sulfate.

The impact of the crystallinity of organic solid materials on their tribocharging propensity is well reported. However, no unequivocal explanation about the potential underlying mechanism(s) could be found so far in the literature. This study reports the effect that different degrees of crystalline disorder has on the tribocharging propensity of a small molecular organic material, salbutamol sulfate (SS). Ball-milling was used to induce structural transformations in the crystalline structure of SS. Particles with different nanostructures were produced and analyzed for their solid-state, particle properties, and tribocharging. It was found that differences in the amorphous content among the processed particles and related moisture levels had an impact on powder tribocharging. A correlation between the latter and the nanostructural properties of the particles was also established. The presence of interfaces between nanodomains of different densities and shorter average lengths within the phases seems to lead to a mitigation of charge. This suggests that undetected, subtle nanostructural differences of materials can affect powder handling and processability by altering their tribocharging. The present findings demonstrate the nanostructural implications of powder triboelectrification, which can help toward the rational design of a wide variety of organic solids.

Establishment of a Molding Procedure to Facilitate Formulation Development for Co-extrudates.

Co-extrusion offers a number of advantages over conventional manufacturing techniques. However, the setup of a co-extrusion line is cost- and time-intense and formulation development is challenging. This work introduces a novel procedure to test the applicability of a co-extruded reservoir-type system at an early product development stage. We propose vacuum compression molding (VCM), a fast procedure that requires only small material amounts, for the manufacturing of cylindrical reservoir-type system. To this end, the commercially available co-extruded product NuvaRing® and variations thereof were used as test systems. All VCM systems showed a homogeneous skin thickness that adhered well to the core, thereby providing a precise core/skin interface. As drug release is a key criterion for pharmaceutical products, a modified in vitro dissolution method was set up to test the VCM systems. The drug release from the VCM systems was in the same order of magnitude as the corresponding co-extruded strands and followed the same release kinetics. Moreover, the VCM systems were capable of indicating the relative effect of formulation-related modifications on drug release. Overall, this shows that this system is a powerful tool that facilitates formulation tailoring and co-extrusion process setup at the earliest stage.