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BACKGROUND
MATERIALS AND METHODS
Moisture Sorption Properties of Different Poloxamer Grades
Daniel J. Burnett1, Armando R. Garcia1, Jerry Y.Y. Heng2, Frank Thielmann3, Yidan Lan4 , Shaukat Ali4, Kai Zhuang4 and Nigel Langley4
1Surface Measurement Systems Ltd., 2125 28th Street SW, Suite 1, Allentown, PA 18103, USA; 2 Department of Chemical Engineering, Imperial College London, UK,
Novartis Pharma AG, Stein Aargau Switzerland, 4 BASF Corporation, Tarrytown, NY10591, USA;
~ Email: dburnett@surfacemeasurementsystems.com, yidan.lan@basf.com ~
Dynamic Vapor Sorption combined with in-situ Raman Spectroscopy (DVS-Advantage, Surface Measurement Systems, UK)
o Automated, gravimetric technique for measuring sorption properties on powders, fibers, granules, films, and other solids
o Readily combined with other in-situ techniques like Raman, Near-IR, and optical microscopy
REFERENCES
1. KolliphorTM P grades, Technical information, BASF (2011)
2. DJ Burnett et al, Int. J. Pharm. 287 (2004), 123
3. A.D. Gift and L.S. Taylor, J. Pharm. Biomed. Anal. 43 14-23 (2007).
4. J. Boullata and V.T. Armenti (editors). Handbook of Drug Nutrient Interactions Nutrition and Health, Springer-Verlag New York , 506-508 (2005)
5. Z. Gu and P. Alexandrildis, J. Dispersion Sci. Tech. 25 619-629 (2004)
6. DJ Burnett, AR Garcia, and F Thielmann, J. Powder Sources, 160: 426-430 (2006)
7. A. E. Haddrel, G. Hargreaves, J. F. Davies and J. P. Reid, Int. J. Pharm. 443 183– 192 (2013)
8. DJ Burnett et al, AAPS Annual Meeting 2014 Poster R6311 (2014)
• The moisture sorption properties of different Poloxamer grades was studied in detail.
• Gravimetric, microscopic, and spectroscopic results clearly indicated a moisture-induced phase change only above 80% RH
at 25 °C.
• Micronized Poloxamer samples show slightly higher water uptake a low RH conditions due to increased surface uptake
• Additional experiments over a broad temperature range could be used to ‘map’ both temperature and humidity conditions
necessary to prevent moisture-induced phase change
• DVS data also demonstrates that Poloxamers can be stored at ambient temperature without any appreciable increase in water
uptake (<2%) at much higher relative humidity conditions
• More studies should be conducted to understand the mechanism how low hygroscopic Poloxamers can enhance the
wettability of drugs [8].
Figure 2. Schematic of DVS-Advantage.
Water sorption properties are crucial for physical characterization of excipients used in pharmaceutical formulation. An important group of excipients is Poloxamers, which are nonionic triblock
copolymers composed of a central hydrophobic block of polypropylene glycol, covalently linked with two hydrophilic blocks of polyethylene glycol on each side. The water sorption isotherms of
Poloxamers are important because of lack of such data in the literature, and relevant to a robust formulation development. In this study, we have investigated the moisture sorption for a range of
Poloxamer grades.
Moisture-Induced Phase Change
CONCLUSIONS
Samples: Poloxamers, a group of triblock copolymers of EO/PO/EO, as shown in Figure 1,
are nonionic surfactants widely used as emulsifiers, wetting agents, control release agents
and solid dispersion carriers in liquid, oral, topical, and parenteral dosage forms [1].
Powdered Poloxamer grades Kolliphor™ P188 & P188 Micro, Kolliphor™ P237, Kolliphor™
P338, Kolliphor™ P407 & P407 Micro (BASF, Ludwigshafen, Germany) were used as
received.
Water sorption properties measured by Dynamic Vapor Sorption (DVS): The DVS
system provides a well-established method for the determination of water sorption and
desorption properties. It has been used successfully in the past to determine the critical
humidity where glass transition and crystallization occurs at constant temperature [2].
Raman Spectra: A unique combination of a fiber optic Raman probe with Dynamic
gravimetric Vapor Sorption (DVS) was used to monitor the real-time transformations using
combined gravimetric and spectroscopic techniques. Raman-vapor sorption experiments
have previously been performed on a wide range of materials [3]. Raman spectra were
obtained by means of i-Raman Plus (B&W Tek, Newark, DE, USA) using a 785nm laser,
and was integrated into the DVS-Advantage instrument directly through a fiber optic probe
and software trigger to collect data during the DVS experiment.
www.surfacemeasurementsystems.com Email: Science@surfacemeasurementsystems.com
Figure 5. Linear humidity ramping experiments for Polaxamer
grades at 25 °C.
Water Sorption Isotherms
Water sorption isotherms for different Poloxamer grades (Figure 4) demonstrate minimal water sorption (less than 2% by mass) up to
80% RH. Above that point, moisture sorption increases exponentially, indicating a sudden change in sorption mechanism, and a rapid
deliquescence at a critical relative humidity of 80%. Although the exact mechanism is not clear, 2% of absorbed water can definitely
dissolve a substantial amount of polymer due to the highly soluble nature of Poloxamers, causing a prompt deliquescence. All six
samples show similar behavior in spite of different particle sizes, and EO / PO values in the polymeric chain. These results are
consistent with the previous data published for Poloxamer P188 [4] and agree with the observation by Gu and Alexandrildis [5].
A close inspection of the moisture sorption isotherms (see insert) indicates some subtle differences. For instance, the ‘Micro’ samples
showed a measurable and slightly higher water sorption capacity compared to their regular grade counterparts. This is most likely due
to the smaller particle size and subsequent higher surface area. Also, the P237 sample appears to be slightly more hydrophilic than the
other Poloxamer grades.
The moisture diffusion rates (Table I) were also measured using the DVS and assuming spherical particle sizes with average diameters
(1000 microns for P188, P237, P338, and P407 samples and 50 microns for P188 micro and P407 micro samples). In general, the
diffusion coefficient goes down as humidity increases. This is most likely due to the surface becoming saturated; thus inhibiting
diffusion, which has been observed previously for other polymers [6].
Figure 4. Water sorption isotherms for Poloxamers at 25 °C (insert
shows data up to 80% RH only).
Humidity ramping experiments were performed on all
Poloxamer grades to more accurately determine the onset
conditions for moisture-induced phase change indicated in
Figure 4. Figure 5 shows a composite plot of all six samples.
The rate of mass change is plotted versus the relative
humidity. Similar experiments have proven effective in
identifying moisture-induced phase transitions on
pharmaceutical materials [2]. All six samples show a
dramatic increase in mass change around 80% RH at 25 °C,
suggesting a critical relative humidity (CRH) for Poloxamer
deliquescence reached at 80% RH.
It is interesting to notice that the low hygroscopic property of
Poloxamer P407 before reaching 80 %RH has been utilized
to suppress the hygroscopic growth for aerosol [7].
Video Microscopy and Raman Spectroscopy
To further study the moisture-induced phase transition indicated by the
isotherm and ramping RH studies, in-situ video images and Raman spectra
were collected during a DVS isotherm experiment (as in Figure 4). Figures 6
and 7 show representative video microscopy data and Raman spectra for the
P188 sample, respectively. Raman spectra of P188 Micro were identical and
did not observe any shifts in the functional group peaks (CH3 (stretching) CH2
(bending) or CO (stretching), regardless of the relative humidity increasing
from 10%, 80% to 90%, which further suggested that the samples remain
unaffected throughout the first order phase transition. Together, these results
clearly indicate visible changes in the sample upon exposure to 90% RH. The
sample changes from a free flowing powder to a gel-like substance between
80% and 90% RH at 25 °C.
Figure 7. Variable RH Raman spectra for P188 Micro sample.
AAPS Annual Meeting, Orlando, FL; October 25-29, 2015; Poster #T3196
Figure 3. Schematic of the DVS stand with Raman adaptor. Figure 1. Structure of Poloxamer.
RESULTS AND DISCUSSIONS
0
10
20
30
40
50
60
0 10 20 30 40 50 60 70 80 90 100
Ch
an
ge
In
Ma
ss
(%
) -
Re
f
Relative Humidity (%)
DVS Isotherm Plot
P188 P237
P338 P407
P188 Micronized P407 Micronized
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
0 10 20 30 40 50 60 70 80
Ch
an
ge
In
Ma
ss
(%
) -
Ref
Relative Humidity (%)
DVS Isotherm Plot
P188 P237
P338 P407
P188 Micronized P407 Micronized
Target RH
[%] P188
P188
Micro P407
P407
Micro P237 P338
20 1.83E-06 2.31E-08 2.04E-06 1.24E-08 1.72E-06 1.57E-06
30 1.52E-06 1.93E-08 2.62E-06 1.34E-08 1.53E-06 1.43E-06
40 1.08E-06 2.10E-08 1.96E-06 1.20E-08 1.30E-06 1.24E-06
50 9.28E-07 1.57E-08 1.40E-06 1.05E-08 1.28E-06 1.12E-06
60 8.10E-07 1.42E-08 9.81E-07 8.56E-09 9.54E-07 7.83E-07
70 4.76E-07 9.48E-09 6.96E-07 5.92E-09 6.05E-07 4.53E-07
80 6.06E-08 9.21E-10 5.92E-08 9.41E-10 2.21E-08 5.80E-08
Table I. Moisture diffusion coefficients for Poloxamer grades at 25 °C.
0
0.005
0.01
0.015
0.02
0.025
0.03
0 10 20 30 40 50 60 70 80 90 100
dm
/dt
(%/m
in)
Relative Humidity (%)
Rate of Mass Change Versus RH
P407 P188 P407 Micro
P338 P237 P188 Micro
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
300 800 1300 1800 2300 2800 3300
Re
lati
ve In
ten
siy
Wave Number (cm-1)
Variable RH Raman Data
P188 Micro 0% RH P188 Micro 80% RH P188 Micro 90% RH
Figure 6. In-situ video images collected on the P188 Micro sample
as a function of RH (0, 80, and 90% RH).