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# Investigation into the effects of high shear blending and storage on powders for inhalation

Willetts, John (2012)
Ph.D. thesis, University of Birmingham.

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## Abstract

Dry powder inhaler (DPI) formulations are usually comprised of a mixture of micronised active pharmaceutical ingredient (API) with aerodynamic diameter 1-5 m to allow deposition in the lower airways, and a coarse (~70 micron) excipient, typically $$\alpha$$-lactose monohydrate, used to aid the handling, metering and dosing of the formulation. These components are usually combined in a secondary manufacturing process such as high shear blending (HSB), which is used primarily to distribute the cohesive drug particles throughout the bulk excipient to create a chemically homogeneous formulation.
This thesis explores the use of HSB to produce mimic DPI formulations and assesses the effect of different blending and storage regimes on various physicochemical properties of such powders. A novel fluidised bed elutriation (FBE) technique was developed to test the ability of fine mimic drug particles to separate from coarse particles in such formulations, along with conventional air jet sieve (AJS) and Next Generation Impactor (NGI) studies. Results showed that, generally, blending regimes were seen to have little effect on the in vitro performance of these mimic formulations, with extended storage at high humidity having a more profound effect on the separation of fine particles. Tests on the performance of formulations using the FBE technique showed that fluidisation performance alone is insufficient to identify blending-induced changes; however, analysis of the fine elutriated fraction has shown subtle changes in the populations of particles due to HSB. Notable differences were observed between the mimic cohesive and adhesive drugs, indicating the ability of these tests to identify formulations with different adhesive properties. In addition, a study to determine the specific energy input (SEI) required to achieve chemical homogeneity suggested that extended high shear blending beyond a given energy input may only alter the size distribution of the formulation, and not improve homogeneity, thus having implications for the manufacture of such products.

Type of Work: Ph.D. thesis. Bridson, Rachel H and Robbins, Phil Colleges (2008 onwards) > College of Engineering & Physical Sciences School of Chemical Engineering QD ChemistryRM Therapeutics. PharmacologyRS Pharmacy and materia medicaTP Chemical technology University of Birmingham 3325
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.

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