“In situ monitoring of pharmaceutical operations”
Author(s)
Osunde, Anthony Osasumwen
Type
Thesis or dissertation
Abstract
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.
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.
Date Issued
2009-03
Date Awarded
2009-03
Advisor
Stepanek, Frantisek
Sponsor
GSK Tonbridge
Creator
Osunde, Anthony Osasumwen
Publisher Department
Department of Chemical Engineering and Chemical Technology
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)