Liquid API feeding in pharmaceutical HME: Novel options in solid dosage manufacturing.

Hot melt extrusion (HME) is a common unit operation. It is broadly applicable in the pharmaceutical industry and can be implemented in a continuous manufacturing line. However, the conventional way of active pharmaceutical ingredient (API) feeding with a pre-blend consisting of a powdered API and a polymer does not allow the flexibility and agility to adjust the process parameters, which is generally an essential part of continuous manufacturing. In addition, this method of API feeding may result in the segregation of the individual powder components or agglomeration of highly cohesive materials, leading to an inhomogeneous API content in the extrudates, especially at low doses. In this study, the universal applicability of liquid side feeding in pharmaceutical HME was demonstrated using various APIs suspended or dissolved in water and fed as suspension or undersaturated, supersaturated, and highly concentrated solutions into anterior parts of the extruder. The extrudates were characterized in terms of their API content, residual moisture content, and solid-state of the API embedded in the polymer. The results show that a uniform API content without major deviations can be obtained via this method. Furthermore, the residual moisture content of the extrudates was low enough to have no significant influence on further processing of the final dosage form. In summary, this advanced way of feeding allows an accurate, flexible, and agile feeding of APIs, facilitating the production of personalized final dosage forms and a novel option to link the manufacturing of the drug substance and the drug product.

On the influence of raw material attributes on process behaviour and product quality in a continuous WET granulation tableting line.

Continuous manufacturing of oral solids is a complex process in which critical material attributes (CMAs), formulation and critical process parameters (CPPs) play a fundamental role. However, assessing their effect on the intermediate and final product's critical quality attributes (CQAs) remains challenging. The aim of this study was to tackle this shortcoming by evaluating the influence of raw material properties and formulation composition on the processability and quality of granules and tablets on a continuous manufacturing line. Powder-to-tablet manufacturing was performed using four formulations in various process settings. Pre-blends of different drug loadings (2.5 % w/w and 25% w/w) and two BCS classes (Class I and II) were continuously processed on an integrated process line ConsiGmaTM 25, including twin screw wet granulation, fluid bed drying, milling, sieving, in-line lubrication and tableting. The liquid-to-solid ratio and the granule drying time were varied to process granules under nominal, dry and wet conditions. It was shown that the BCS class and the drug dosage influenced the processability. Intermediate quality attributes, such as the loss on drying and the particle size distribution, directly correlated with the raw material's properties and process parameters. Process settings had a profound impact on the tablet's hardness, disintegration time, wettability and porosity.

SEDEX-Self-Emulsifying Delivery Via Hot Melt Extrusion: A Continuous Pilot-Scale Feasibility Study.

The aim of this study was to develop a continuous pilot-scale solidification and characterization of self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME) using Soluplus® and Kollidon® VA-64. First, an oil-binding capacity study was performed to estimate the maximal amount of SEDDSs that the polymers could bind. Then, HME was conducted using a Coperion 18 mm ZSK18 pilot plant-scale extruder with split-feeding of polymer and SEDDS in 10, 20, and 30% w/w SEDDSs was conducted. The prepared extrudates were characterized depending on appearance, differential scanning calorimetry, wide-angle X-ray scattering, emulsification time, droplet size, polydispersity index, and cloud point. The oil-binding studies showed that the polymers were able to bind up to 50% w/w of liquid SEDDSs. The polymers were processed via HME in a temperature range between 110 and 160 °C, where a plasticizing effect of the SEDDSs was observed. The extrudates were found to be stable in the amorphous state and self-emulsified in demineralized water at 37 °C with mean droplet sizes between 50 and 300 nm. A cloud point and phase inversion were evident in the Soluplus® samples. In conclusion, processing SEDDSs with HME could be considered a promising alternative to the established solidification techniques as well as classic amorphous solid dispersions for drug delivery.