Transcript AAPS Pster - Drake University

Solubility of Carbamazepine in Aqueous Solutions of Sodium Dodecyl Sulfate
Andrew Davis, Dorothy Chrzaszcz, Maria Bohorquez, Nita Pandit
College of Pharmacy, Drake University, Des Moines, IA
Department of Chemistry, College of Arts and Sciences, Drake University, Des Moines, IA
Poorly water soluble drugs can be delivered in
pharmaceutical formulations in higher
concentrations by using surfactants.
We are interested in enhancing the solubility of
the antiepileptic drug carbamazepine (CMZ), by
using surfactants.
We have used the anionic surfactant sodium
dodecyl sulfate (SDS) as a model surfactant for
solubilization studies.
The solubility of CMZ in water and in varying
concentrations of SDS was determined by
spectrophotometric analysis at room
temperature.
METHODS
RESULTS
Solubility Study
Solubility Ratio as a Function of SDS
Concentration
70
Calibration Curve
Solutions of 0, 3, 6, 10, 20, 40, 60, and 80 mM SDS in water were
prepared. 3mLs of each solution were added to a test tube, and
sufficient solid carbamazepine was added to saturate the solutions.
Each concentration was prepared in triplicate. The solutions were
allowed to equilibrate for no less than 7 days at 24° C. Solutions were
then passed through a 0.45µm filter to remove excess un-dissolved
drug. This was followed by appropriate serial dilutions with ethanol.
Diluted samples were then read spectrophotometrically. The solubility
of CMZ in each solution was calculated.
60
Solutions of varying concentrations of CMZ were prepared in
water. The solutions were read with a Beckman DU 7500
UV-Vis diode array spectrophotometer. The absorbance at
286 nm was plotted against the concentration to prepare a
calibration curve. The slope of the linear regression line
(11,714) gives the molar absorptivity of CMZ in water at
286nm.
Absorbance
1
0.5
ε = 11,714
5
10
15
20
Concentration of CMZ (M x 10-4)
Beer’s Law describes the dependence of absorbance (A) on molar
absorptivity (ε), concentration (C), and the path length of the light (l).
A= ε l C
1.5
1.09
10
4.19
20
12.8
40
33.26
60
41.04
80
59.84
20
40
60
80
100
Our observations show that the aqueous solubility of CMZ at 26°C is
4.23 x 10-4 M. The solubility of CMZ increases as a function of SDS
concentration above the critical micelle concentration (cmc). For
example, CMZ solubility is 4.2 times greater in 10mM SDS, 12.8
times greater in 20 mM SDS, and 59.8 times greater in 80mM SDS.
Very little solubility enhancement is seen at SDS concentrations below
the cmc.
FUTURE WORK
1
ε = 10,712
0
In the future, alternative surfactants such as Pluronic F127 will be
analyzed to quantify their solubilizing properties for carbamazepine.
0.5
1
1.5
2
2.5
Concentration CMZ (M x 10-4)
REFERENCES
1.00
0.95
0.90
0.85
0.80
0.75
0.70
0.65
0.60
0.55
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
60 mm SDS
40 mm SDS
20 mm SDS
10 mm SDS
0 mm SDS
Carbamezepine Solubility as a Function of
SDS Concentration
-2
250
275
300
Wavelength nm
325
350
10-23-2005
A Study of the Temperature-Dependent Micellization of Pluronic F-127.
Bohorquez, et al. Journal of Colloid and Interface Science 1999.
3.00
Concentration of Carbamezapine (M) x10
Absorbance
Spectra of Carbamazepine in SDS Solutions
Carbamazepine
6
The results confirm that SDS micelles can solubilize CMZ and
significantly increase its total aqueous solubility.
0
Carbamazepine (CMZ) is a hydrophobic drug used
for its antiepileptic properties. It has a MW of
236.30.
1.08
2
0.5
http://en.wikipedia.org/wiki/Micelle
3
2.5
SDS micelles
http://www.psc.edu
1
The cmc of SDS has been confirmed as in other studies at
approximately 8mM at room temperature.
Calibration Curve of Carbamazepine in
Ethanol
Abssorbance
Sodium Dodecyl Sulfate
C12H25SO4Na
•MW of 288.38
• anionic
•forms micelles
•used to enhance solubility
1.5
0
10
0
CONCLUSIONS
2
0
20
Concentration
Ratio
SDS Concentration (mM)
2.5
Surfactants are present in everyday substances like soaps
and detergents. They are composed of hydrophobic
and hydrophilic portions. The surfactant molecules aggregate
to form a micelle with a hydrophobic interior and
hydrophillic exterior. Non polar drugs and other solutes can
be solubilized in the micelle.
30
0
Calibration Curve of Carbamazepine in
Water
BACKGROUND
40
SDS
Concentration
(mM)
0
A calibration curve in ethanol was also prepared in the same
manner.
Spectrophotometric Analysis
50
Stotal/Swater
OBJECTIVES
2.50
Dissolution Media for In Vitro Testing of Water-Insoluble Drugs: Effect of
Surfactant Purity and Electrolyte on In Vitro Dissolution of Carbamazepine
in Aqueous Solutions of Sodium Lauryl Sulfate. Crison, Weiner, Amidon.
Journal Of Pharmaceutical Sciences 1997.
2.00
1.50
1.00
Surfactant-Mediated Dissolution: Contributions of Solubility Enhancement
And Relatively Low Micelle Diffusivity. Balakrishnan, et al. Journal of
Pharmaceutical Sciences 2004.
0.50
0.00
0
20
40
60
80
100
SDS Concentration (mM)
Presented 4-27-2006