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Title: In situ monitoring of pharmaceutical operations
Author: Osunde, Anthony Osasumwen
ISNI:       0000 0004 2686 8588
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2009
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The subject of the thesis is the examination of the phenomena behind the formulation and spatio-temporal evolution of anisotropic particle assemblies during drying processes. Two different drying processes have been investigated in this study, namely spray drying and contact drying. Following a literature review of the relevant processes – namely spray drying but also particle agglomeration and break-up, literature on the packing of non-spherical particles is reviewed. An investigation into the effect of particle shape, solubility, initial concentration and state (solution vs. slurry), and drying rate on the microstructure of particle assemblies within an evaporating droplet has been carried out. The materials used in the study 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 and water. The study of single droplet drying aims to provide a quantitative and qualitative view on the microstructure formation during drying. A new single droplet drying technique has been developed to allow for real-time observation of the microstructure and morphology evolution, and subsequently to determine whether the particle morphologies produced in single droplet drying are analogous to those produced by a spray dryer. The results produced in this study indicate that for the materials investigated, the end microstructural arrangement obtained by the 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 likely particle morphology. This has significance during process scale-up in the pharmaceutical industry and in other situations when only small quantities of a newly developed chemical entity 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 drying mechanism behind the morphologies commonly produced in spray drying.
Supervisor: Stepanek, Frantisek Sponsor: GSK Tonbridge
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral