Amorphous Solid Dispersions (ASDs): The Influence of Material Properties, Manufacturing Processes and Analytical Technologies in Drug Product Development.

Poorly water-soluble drugs pose a significant challenge to developability due to poor oral absorption leading to poor bioavailability. Several approaches exist that improve the oral absorption of such compounds by enhancing the aqueous solubility and/or dissolution rate of the drug. These include chemical modifications such as salts, co-crystals or prodrugs and physical modifications such as complexation, nanocrystals or conversion to amorphous form. Among these formulation strategies, the conversion to amorphous form has been successfully deployed across the pharmaceutical industry, accounting for approximately 30% of the marketed products that require solubility enhancement and making it the most frequently used technology from 2000 to 2020. This article discusses the underlying scientific theory and influence of the active compound, the material properties and manufacturing processes on the selection and design of amorphous solid dispersion (ASD) products as marketed products. Recent advances in the analytical tools to characterize ASDs stability and ability to be processed into suitable, patient-centric dosage forms are also described. The unmet need and regulatory path for the development of novel ASD polymers is finally discussed, including a description of the experimental data that can be used to establish if a new polymer offers sufficient differentiation from the established polymers to warrant advancement.

Applicability of image analysis to support QbD driven development of pellets.

OBJECTIVE: The stages of preparing high drug loaded pellets were investigated using static and dynamic imaging techniques to provide a greater understanding and ease the scale up process. SIGNIFICANCE: An example of a real case laboratory and production scale quality by design (QbD) based development of pellets is demonstrated. Potential process analytical technology (PAT) approaches by dynamic image analysis (DIA) are presented in various process phases. METHODS: Pellets were prepared at laboratory and production scale (high shear granulation, extrusion/spheronization, drying, and coating). The influence of process parameters on pellet properties (aspect ratio (AR), yield, pellet size, and their distribution) was investigated using static and DIA. During coating, we focused on the coating thickness and identification of potential agglomeration. RESULTS AND CONCLUSION: The effects of kneading time, amount of water, extrusion screen plate (ESP) opening diameter and thickness on pellet properties were confirmed in accordance with literature. In terms of screw speed, spheronization speed and time, no considerable influence on pellet properties was observed in the range of studied process parameters, thereby confirming the design space. In addition to the ESP thickness and opening diameter, quality of the ESP impacts the pellet properties. Lastly, coating thickness measurements with dynamic and static image analysis were comparable and an exemplary case of in-line agglomeration detection was presented. Real-time evaluation with PATVIS APA is an effective PAT tool for the evaluation of spheronization (pellet size distribution, AR, and yield) and coating (coating thickness, agglomeration detection).

Granular Matter Transport in Vertical Pipes: The Influence of Pipe Outlet Conditions on Gravity-driven Granular Flow.

Gravity transport of granular materials in vertical pipes is one of the most fundamental steps in bulk powder handling and processing. Presented study investigates powder flow characteristics in vertical pipes with open and closed outlets and condition of free powder fall. Powder flow of pharmaceutical grade powders was observed in transparent, vertical pipe model. Description of flow structures was performed. Powder volume flow rate, acceleration, and dilatation were quantified and correlated with powder properties. The results show that in pipes with a closed outlet the escaping air slows down the powder flow, resulting in a much slower flow than in pipes with an open outlet. A dense granular flow was detected in an open outlet condition, whereas in a closed outlet condition two concurrent flow regimes were observed: a slow moving, dense powder bed, and a fast dilute powder flow. Differences in flow regimes may promote segregation, with important implications to industrial processes.