the effect of ethanol - sciforumsciforum.net/conference/ecps2011/paper/530/download/slides.pdf ·...
TRANSCRIPT
2/19/2011
1
The effect of Ethanol
• Various solid state composition
• Depends on the spray dry conditions (i.e temperature, humidity)
Polymorphism
2/19/2011
2
Aims
Assess if polymorphic change follows the trend linked tothe particle size distribution that is normally obtainedduring spray dry process.
To investigate the effect of ethanol on drying kinectics,which then affect the crystal growth and dryingbehavior of polymorphs .
Methods
MATERIALS
• D-Mannitol
α,β,δ and
hemihydrate
• Ethanol
DATA INTERPRE-TATION
Identify polymrphic
change according to particle size
4
Raman Microscopy
CHEMO-METRICS
Multivariate Data Analysis
PLS-DA
SPRAY DRY
Mannitol in 10% Ethanol
1
NGI
Separate to different particle
size fractions
(Stage 1 – Stage 8)
2
SOLID STATE ANALYSIS
Characterize mannitol
polymophrs
3
X-RAY Diffracto-
metry
Scanning Electron
Micrograph / Thermogravi-
metric Analysis
2/19/2011
3
Results – SEM / TGA
Stage 110.9 ± 3.4 µm
Stage 42.7 ± 1.7 µm
Stage 7,81.0 ± 0.4 µm
TGA - No detectable weight loss
Results - XRD
5 10 15 20 25 30 35 40
Offset Y
valu
es
2 Theta
S78
S6
S5
S4
S3
S2
S1
Bulk
10% Ethanol
αα ββ
• All samples contain α and β-mannitol.
• Comparing the ratio of two polymorphs at indicated positions, αcontents increase relatively at smaller particle size.
Bulk
Stage 1
Stage 2
Stage 3
Stage 4
Stage 5
Stage 6
Stage 7,8
2/19/2011
4
Results – Raman Microscopy
400 600 800 1000 1200 1400
0
5000
10000
15000
20000
25000
30000
Inte
nsity
Wavenumber (cm-1)
alpha mannitol
beta mannitol(a)
400 600 800 1000 1200 1400
-0.15
-0.10
-0.05
0.00
0.05
0.10
0.15
Wavenumber (cm-1)
Loading 1, 86.54%
Loading 2, 13.15%
Loading 3, 0.25%
(b)
• 3 principal components• 100% specificity and sensitivity• 0% misclassification rate
Results – Raman Microscopy
-- Bulk powder -- S 1 S 2 S 3 S 4 S 5 S 6 S 7 S 8
0
10
20
30
40
50
60
70
80
90
100
Perc
en
tag
e o
f b
eta
ma
nn
ito
l (%
)
NGI stage
(c)
• Content of β-mannitoldecreased from NGI Stage 1 to 8
2/19/2011
5
Different drying rates for droplets with various sizes
1 sec 5 secs
• Smaller droplets are likely to dry faster than larger droplets
• Ostwald rules of stages– more meta-stable α-mannitol in small particles
• Moisture as ‘lubricant’ for stable crystal arrangement– more stable β-mannitol in large particles
Conclusions
• Ethanol increases drying rate of mannitol in thespray drying system, leading to the presence ofmeta-stable α-mannitol in addition to stable β-mannitol.
• Polymorphic form of mannitol changes accordingto particle size from spray drying process.