(340d) Analysis of the Microstructure of Particles Obtained By Evaporating Acoustically Levitated Single Droplets Using X-Ray Computed Tomography
AIChE Annual Meeting
2019
2019 AIChE Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Innovations in Particle Engineering: From Amorphous Solid Dispersions to New Processing
Tuesday, November 12, 2019 - 1:33pm to 1:54pm
Hassan Abdullahi Hassan Abdullahi 4 6 2019-04-20T00:43:00Z 2019-04-20T00:47:00Z 1 576 3289 University of Manchester 27 7 3858 14.0
Clean Clean false false false false EN-GB JA X-NONE
Analysis
of the microstructure of particles obtained by evaporating acoustically
levitated single droplets using X-ray computed tomography
normal">
mso-bidi-font-family:Calibri">1
normal">School
of Chemical Engineering and Analytical Science, University of Manchester,
Manchester, UK;
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110%;font-family:Calibri">Eli Lilly
normal">
& Company, Indianapolis, IN, USA
font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:
" ms pgothic mso-bidi-font-weight:bold>thomas.vetter@Manchester.ac.uk
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char">The flowability and tabletability ofpowders is an important consideration in the manufacturing of pharmaceutical
products. These properties can be successfully tuned by crystallising particles
of a desired morphology, or, more flexibly, by engineering the microstructure
of the individual particles in a spray drying process it can be tuned by
altering the formulation and process conditions [1][2]. Therefore,
spray drying offers a unique opportunity to design tailor made particles in a
single step process involving simultaneous droplet drying and particle
formation. However, carrying out an in-depth investigation of particle
morphology and microstructure directly on the scale of a typical spray dryer
(that contains millions of droplets at any time) is infeasible. Instead, single
droplet studies are often used to understand how drying conditions affect the
microstructure of the resulting dried particles [3][4]. In the present work, mso-ansi-language:EN-US">an acoustic levitation approach is used to suspend
single droplets in an atmosphere of controlled relative saturation and
temperature (Figure 1). Through a camera and automated image analysis, we study
the droplet drying dynamics, as well as the macroscopic morphology of the
resulting particle. We have further applied Raman spectroscopy and scanning electron
microscopy to study the solid state form, as well as
the surface characteristics. By applying X-ray computed tomography, we have
elucidated the internal microstructure of the formed particles and have uncovered
a fascinating variety of structures, depending on the mixture dried (we have
investigated combinations of different solutes, solvents, and polymers acting
as excipients), as well as the processing conditions (temperature and relative
saturation of nitrogen used as drying gas). The results can be correlated with
formulation and process conditions to produce drying maps for different
systems. Calibri"> line-height:125%;layout-grid-mode:char"> 11.0pt;line-height:125%;font-family:Cambria;mso-ascii-theme-font:minor-latin;
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Figure SEQ Figure \* ARABIC 1: Suspension of a droplet in a controlled atmosphere using an acoustic levitator.
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Calibri">The droplet drying history during evaporation is shown in Figure 2a
for an aqueous formulation of mannitol (4.5 wt%) and PVP (0.9 wt%). In the
first drying stage, the diameter of the droplet decreases as solvent is
evaporated from the droplet surface. In the second drying stage, a shell forms
and evaporation occurs through interstices in the shell. The evaporation rate
hence reduces significantly due to the added resistance of the crust. When
presented as a plot of normalised squared diameter
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against time, the two drying regimes can
be clearly identified. We have performed such characterisation for a variety of
process conditions and the particles obtained can be subsequently analysed to
provide useful information on particle properties such as size, shape,
porosity, roughness and crystal structure. Figure 2b and 2c shows exemplary
images of particles obtained using SEM and micro X-ray computed tomography. By
investigating the droplet drying dynamics and resulting particle microstructure,
for a variety of mixtures and operating conditions enables us to gain deep
insight into the process behaviour and the properties of the resulting particles.
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Figure 2: a) Droplet drying history and particle obtained from drying an aqueous formulation containing 0.9%w/w polymer, 4.5%w/w mannitol at 60C and 0% relative humidity b) SEM image c) cut-away surface from micro X-ray tomography.
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mso-ascii-theme-font:minor-latin;mso-fareast-font-family:" ms pgothic mso-hansi-theme-font:minor-latin>References
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