No abstract

No abstract

The melt-extrusion process is currently applied in the pharmaceutical field in the manufacturing of a variety of dosage forms and formulations, including solid dispersions. Though this technology is considered efficient and continuous, there are potential challenges of which, additional thermal degradation of drug substance because heat stress and shear forces are of a primary concern. This paper attempts to understand the impact of thermal and/or mechanical components of the melt-extrusion process on the stability of a thermosensitive drug substance during scale-up. The overall degradation profile of the drug substance was correlated with the various physical changes made to the extruder as well as the process temperature. The results suggested that the degradation profile of a thermosensitive drug substance could be controlled by proper design of screw assemblies and by optimization of screw rotations per minute, process temperature, and feed rate during development and scale-up.

No abstract

The primary goal of this study was to evaluate the use of specific surface area as a measurable physical property of materials for understanding the batch-to-batch variation in the flow behavior. The specific surface area measurements provide information about the nature of the surface making up the solid, which may include defects or void space on the surface. These void spaces are often present in the crystalline material due to varying degrees of disorderness and can be considered as amorphous regions. In the present work, the specific surface area for 10 batches of the same active pharmaceutical ingredient (compound 1) with varying quantity of amorphous content was investigated. Some of these batches showed different flow behavior when processed using roller compaction. The surface area value was found to increase in the presence of low amorphous content, and decrease with high amorphous content as compared to crystalline material. To complement the information obtained from the above study, physical blends of another crystalline active pharmaceutical ingredient (compound 2) and its amorphous form were prepared in known proportions. Similar trend in specific surface area value was found. Tablets prepared from known formulation with varying amorphous content of the active ingredient (compound 3) also exhibited the same trend. A hypothesis to explain the correlation between the amorphous content and specific surface area has been proposed. The results strongly support the use of specific surface area as a measurable tool for investigation of source of batch to batch variation in processability.