1. © File copyright Colin Purrington. You may
use for making your poster, of course, but
please do not plagiarize, adapt, or put on
your own site. Also, do not upload this file,
even if modified, to third-party file-sharing
sites such as doctoc.com. If you have
insatiable need to post a template onto your
own site, search the internet for a different
template to steal. File downloaded from
http://colinpurrington.com/tips/academic/po
sterdesign.
Introduction
The new approach of incorporation of surfactants in
amorphous solid dispersions can be applied for poorly
water-soluble drugs. It relatively increases the
dissolution rate and the apparent solubility. Hence, the
bioavailability of the orally administered drug is
increased [1]. According to Noyes and Whitney
equation, the increase in dissolution rate can be
achieved by increasing the surface area of a drug [2].
Solid dispersions containing surfactants proves to have
an affect on surface area and solubility. Furthermore,
the solubility of the drug is very much governed by the
interactions of drug molecules with the neighbouring
molecules [3]. If a crystal lattice is formed, it will have
a relatively lower solubility than the one of amorphous
form. This is due to higher Gibb’s energy of the
amorphous form [4] [2].
The ball milling technique was applied to prepare a
solid dispersions containing a model drug griseofulvin
(GF) with hydroxypropylmethylcellulose acetate
succinate (HPMCAS). Three different surfactants,
sodium dodecyl sulfate (SDS),
dodecyltrimethylammonium bromide (DTAB) and
Pluronic F127 were incorporated in a solid dispersions.
The prepared formulations then were characterized
using spectroscopic and thermal analysis methods.
Materials and methods
Preparation of solid dispersions by ball milling
Mixtures of around 1g of the same ratio (1:1) GF and
HPMCAS, and varying amounts of SDS, DTAB and F127
surfactants were ball milled using ceramic balls for 2,
4, 6, 8, 10 and 15 minutes. Prepared dispersions were
kept in a desiccator until further analysis.
Characterisation of solid dispersions
Differential Scaning Calorimetry (SDC)
Around 10 mg of a sample was loaded into aluminum
pans, which were hermetically sealed with a lid pin
holed . The sealed pans were heated at a rate of
10ºC/min from 25ºC to 90 ºC, where samples were
held for 10 min in order to remove any moisture. Then
they were cooled at 25ºC and heated up to 250ºC at
the same rate.
Fourier transform infrared spectroscopy (FT-IR)
Spectra was recorded at room temperature (298K) in
the region 4000-550 cm -1 . Scan number was 64 and a
resolution 4 cm -1. The background scan was performed
before the analysis and after every three sample
measurements.
UV/Vis spectroscopy
The saturation solubility was determined using a
standard GF calibration curve at a maximum
absorbance of GF at 295 nm.
Scanning Electron Microscopy (SEM)
Scanning electron images were produced using
Acknowledgments
The author would like to thank Hisham Al-Obaidi for a help, support and advice on this
project. Also, the Centre for Ultrastructural Imaging , King’s College London, Guy’s
Campus, for help with SEM instrument.
conductive carbon adhesive tape on a aluminum stub
and coated with gold for around 2 min at 30 mA.
Laser diffraction
Particle size was measured using laser diffraction at
600 nm. 6.8 buffer solution(10ml) was used to dissolve
around 5 mg of drug powder.
Results
The DSC, SEM, particle size and solubility results are
displayed below.
From the solubility studies it can be seen that there is a
correlation between the sample size and a saturation
solubility of griseofulvin (Fig.1 and Fig. 2) As an
example, saturation solubility was highest for the
samples that contained SDS surfactant. The reason for
this is smaller particle size and higher surface area.
Fig. 1. Particle size (in µm) of the samples with 1% of surfactant
Fig.2. Saturation solubility ( in mg/ml) of GF with 1% surfactant
Fig.3. DSC thermogram of GF/HPMCAS/1%DTAB milled solid dispersions
The heat of fusion, melting temperature and heat of
crystallization of solid dispersions was determined
using DSC. The thermogram of different samples with
different milling times were produced. As can be seen
in Fig.3., there is a slight shift of the peaks with
increasing ball milling time. The reduction of melting
temperature resulted from lower crystalline content of
GF.
Scanning electron images (Fig.4.) shows a particle size
and represents a morphology of different samples.
Fig. 4. Scanning electron images (3000x) of 10 min ball milled
GF/HPMCAS with (a) 1% SDS, (b) 1% DTAB, (c) 1% F127 and (d) No
surfactant
Conclusions
Ball milling was used to prepare solid dispersions of
griseofulvin. The properties of hydrophylic polymer
HPMCAS made it suitable carrier for these
preparations. Successful incorporation of surfactants
show a significant difference in solubility and stability
of the drug. The saturation solubility was highest when
1% SDS surfactant was used. However, it decreased
with increasing amount of surfactant, most likely due
to decrease in surface activity. The DSC data showed a
decrease in melting temperature with increased ball
milling times of the samples. This suggests that the
sample had a higher ratio of amorphous material than
crystalline. The FT-IR proved to be a great technique
for analysis of molecular interactions . The results
confirmed the presence of hydrogen bonding between
the drug and the polymer.
Ieva Petraityte, Hisham Al-Obaidi
Institute of Pharmaceutical Science, King’s College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom
References
[1] N. Wyttenbach, C. Janas. Miniaturised screening
of polymers for amorphous drug stabilization
(SPADS): Rapid assessment of solid dispersion
systems. EuropJourPharm. 2013, 84, 583-598.
[2] S. A. Mogal, P. N. Gurjar. Solid dispersion
technique for improving solubility of some poorly
soluble drugs. DerPharmaciaLettre. 2012, 4(5),
1574-1586.
[3] N. A. Urbanetz, B. C. Lippold. Solid dispersions of
nimodipine and polyethylene glycol 2000:
dissolution properties and physic-chemical
characterisation.EuropJourPharm.2005, 59, 107-
118.
[4] P. Karmwar, K. Graeser. Investigation of properties
and recrystallisation behaviour of amorphous
indomethacin samples prepared by different
methods. InterJourPharm. 2011, 417, 94-100.
(a)
(c) (d)
0
0.2
0.4
0.6
0.8
1
1.2
1.4
SDS DTAB F127 No Surfactant
Aqueoussolubilitymg/ml
Samples of different ball milling times
Saturation solubility of griseofulvin with 1%
of surfactant
2 min BM
4 min BM
6 min BM
8 min BM
10 min BM
15 min BM
0
5
10
15
20
25
30
35
40
45
50
SDS DTAB F127 No surfactant
Particlesize(µm)
Samples of different ball milling times
Particle size of samples with 1% of surfactant
2 min BM
4 min BM
6 min BM
8 min BM
10 min BM
15 min BM
(a) (b)
(c) (d)