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.
Highlights
Oral drug delivery is the favoured route of drug delivery, due to the convenience of administration, being non-invasive and more likely to promote patients compliance with their treatments [1]
Efficient and reproducible blending process is critical to manufacturing of oral drug delivery systems, as the quality of the final product is driven by the quality of the blend
The work in this study aims to investigate the impact of blending technique, excipient characteristics and dilution potential of three model excipients on developing a uniform blend comprising of small dose model active pharmaceutical ingredient (API), ergocalciferol
Summary
Oral drug delivery is the favoured route of drug delivery, due to the convenience of administration, being non-invasive and more likely to promote patients compliance with their treatments [1]. Production of non-homogenous blends results in discrepancy in the content of the active pharmaceutical ingredient (API) and product failure [2]. Blending is a process where two ingredients or more are processed in order to achieve a homogenous product [3, 4]. Three main mechanisms of powders blending are involved; convection, diffusion, and shear. Convective blending encompasses gross movement of particles within the blend, whereas, diffusion is a slow blending process where individual particles are distributed upon blending into newly formed interface. The shear mechanism of blending comprises of blending material while passing along forced slip planes which could aid in breaking agglomerates and enable blending [4,5,6]. Blending of cohesive materials is more complex because of the possibility of developing aggregates and lumps [3, 4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
