In situ monitoring of pharmaceutical operations
Author(s)
Osunde, Anthony Osasumwen
Type
Thesis
Abstract
The subject of the thesis is the examination of the phenomena behind the formulation andspatio-temporal evolution of anisotropic particle assemblies during drying processes. Twodifferent drying processes have been investigated in this study, namely spray drying andcontact drying. Following a literature review of the relevant processes ? namely spray dryingbut also particle agglomeration and break-up, literature on the packing of non-sphericalparticles is reviewed. An investigation into the effect of particle shape, solubility, initialconcentration and state (solution vs. slurry), and drying rate on the microstructure of particleassemblies within an evaporating droplet has been carried out. The materials used in thestudy were chosen so as to cover a range of solubility and crystal shape, and include:benzoic acid (needle shaped) and glass beads (spherical shape), monosodium glutamate(MSG), lactose, hydroxypropylmethylcellulose (HPMC), aspirin, sodium carbonate andwater.The study of single droplet drying aims to provide a quantitative and qualitative view on themicrostructure formation during drying. A new single droplet drying technique has beendeveloped to allow for real-time observation of the microstructure and morphology evolution,and subsequently to determine whether the particle morphologies produced in single dropletdrying are analogous to those produced by a spray dryer. The results produced in this studyindicate that for the materials investigated, the end microstructural arrangement obtained bythe single droplet technique will be essentially the same as that obtained in a spray dryer,and the single droplet method can therefore be used as an early indication of the most likelyparticle morphology. This has significance during process scale-up in the pharmaceuticalindustry and in other situations when only small quantities of a newly developed chemicalentity are available but a decision about the process route has to be made at an early stage.The single droplet results have also allowed for the understanding of some dryingmechanism behind the morphologies commonly produced in spray drying.
Date Issued
2009-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Creator
Osunde, Anthony Osasumwen
Publisher Institution
Imperial College London (University of London)
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)