Determination of process variables affecting drug particle attrition within multi-component blends during powder feed transmission

Abstract

The aim of this study was to determine the location of attrition of formulated API particles within a powder feed system using a Morphologi G3-ID system, an image analyzer with integrated Raman capability enabling classification of particles with respect to their chemistry, to extract the API size distribution from the blended sample. The study also aimed to investigate the impact of other process variables, such as feed screw speed, on the extent of attrition observed. The study demonstrated that attrition occurs in two zones of the powder feed system, at the bottom of the hopper at the interface with the feed screw, and also within the feed screw itself. In the situation of the attrition at the bottom of the hopper variations in the hopper fill level were not observed to change the extent of attrition observed. Variation of the feed screw speed was observed to affect the extent of API attrition, with the particle size within the formulation observed to decrease with increasing speed. The findings highlight that an understanding of the impact of unit processes, and variations in the associated processing conditions, is vital in order to fully understand the behavior and performance of pharmaceutical dosage forms.

Enhanced Understanding of Pharmaceutical Materials Through Advanced Characterisation and Analysis

“…The API at this stage is typically characterised prior to inclusion in a formulated blend ready for preparation of a final drug product, often with the assumption that the input powder characteristics represent that of the API in the final dosage form. Recent applications of integrated image analysis/spectroscopic tools has provided a means to directly determine the size (and shape) of API particles within formulated samples demonstrating that this assumption is not always appropriate (30)(31)(32)(33) and may indeed have an impact on the downstream processability (e.g. sticking) of such formulations (34).…”

Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

“…Regarding the topic of material transfer in solid dosage form manufacturing, it might also be noted that segregation events may potentially be induced by changes in the original particle size due to attrition. For instance, a developmental API has been found to undergo bulk fragmentation and a size reduction during the feeding in a horizontal screw feeder even though it resisted comminution in a tumbling blender and conical mill [43,44] Other reports have described the granules' attrition in continuous twin screw granulation lines, namely during the transfer of wet granules to the fluid bed dryer and at the transfer line of dried granules. The effect of a diminished 'oversized' fraction and an increased fine content was more pronounced for pneumatic conveyance lines than for gravitational transfer, and the susceptibility of the dry material to breakage was related to formulation composition and final moisture content, so that the drying process needed to be optimized for the generation of sufficiently solid bonds for the material to resist comminution [45,46].…”

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

“…The use of this technique is aligned with proposals for improving the understanding of particle performance, and product critical quality attributes (CQA's), in developing pharmaceuticals. 38 Sample dispersion and imaging approaches were aligned to the nature of the material being analysed, as published in previous work 29,[39][40][41][42] . In order to remove partially imaged and overlapping particles morphological filtering of the raw image data was conducted using a combination of convexity and solidity filters, according to previous studies 29,33,38,39,43 .…”