Powder blend homogeneity is a critical attribute in formulation development of low dose and\npotent active pharmaceutical ingredients (API) yet a complex process with multiple contributing\nfactors. Excipient characteristics play key role in efficient blending process and final\nproduct quality. In this work the effect of excipient type and properties, blending technique\nand processing time on content uniformity was investigated. Powder characteristics for\nthree commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose)\nwere initially explored using laser diffraction particle size analyser, angle of repose for\nflowability, followed by thorough evaluations of surface topography employing scanning\nelectron microscopy and interferometry. Blend homogeneity was evaluated based on content\nuniformity analysis of the model API, ergocalciferol, using a validated analytical technique.\nFlowability of powders were directly related to particle size and shape, while surface\ntopography results revealed the relationship between surface roughness and ability of\nexcipient with high surface roughness to lodge fine API particles within surface groves\nresulting in superior uniformity of content. Of the two blending techniques, geometric blending\nconfirmed the ability to produce homogeneous blends at low dilution when processed for\nlonger durations, whereas manual ordered blending failed to achieve compendial requirement\nfor content uniformity despite mixing for 32 minutes. Employing the novel dry powder\nhybrid mixer device, developed at Aston University laboratory, results revealed the superiority\nof the device and enabled the production of homogenous blend irrespective of excipient\ntype and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using\nnon-sieved excipients and the dry powder hybrid mixing device enabled the development of\nsuccessful blends within compendial requirements and low relative standard deviation.
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