An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug

Hamad Alyami, Eman Dahmash, James Bowen, Afzal Mohammed

Research output: Contribution to journalArticle

Abstract

Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1% and 0.5% w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.  
Original languageEnglish
Article numbere0178772
Number of pages19
JournalPLoS ONE
Volume12
Issue number6
DOIs
Publication statusPublished - 13 Jun 2017

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Excipients
Particle Size
particle size
Powders
Particle size
drugs
powders
dosage
Processing
Pharmaceutical Preparations
ingredients
Surface topography
surface roughness
Equipment and Supplies
Starch
Dilution
topography
Surface roughness
methodology
Interferometry

Bibliographical note

© 2017 Alyami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite this

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title = "An investigation into the effects of excipient particle size, blending techniques and processing parameters on the homogeneity and content uniformity of a blend containing low-dose model drug",
abstract = "Powder blend homogeneity is a critical attribute in formulation development of low dose and potent active pharmaceutical ingredients (API) yet a complex process with multiple contributing factors. Excipient characteristics play key role in efficient blending process and final product quality. In this work the effect of excipient type and properties, blending technique and processing time on content uniformity was investigated. Powder characteristics for three commonly used excipients (starch, pregelatinised starch and microcrystalline cellulose) were initially explored using laser diffraction particle size analyser, angle of repose for flowability, followed by thorough evaluations of surface topography employing scanning electron microscopy and interferometry. Blend homogeneity was evaluated based on content uniformity analysis of the model API, ergocalciferol, using a validated analytical technique. Flowability of powders were directly related to particle size and shape, while surface topography results revealed the relationship between surface roughness and ability of excipient with high surface roughness to lodge fine API particles within surface groves resulting in superior uniformity of content. Of the two blending techniques, geometric blending confirmed the ability to produce homogeneous blends at low dilution when processed for longer durations, whereas manual ordered blending failed to achieve compendial requirement for content uniformity despite mixing for 32 minutes. Employing the novel dry powder hybrid mixer device, developed at Aston University laboratory, results revealed the superiority of the device and enabled the production of homogenous blend irrespective of excipient type and particle size. Lower dilutions of the API (1{\%} and 0.5{\%} w/w) were examined using non-sieved excipients and the dry powder hybrid mixing device enabled the development of successful blends within compendial requirements and low relative standard deviation.  ",
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AU - Mohammed, Afzal

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