Supplementary Information
FACTORS AFFECTING DRUGS ADSORPTION ON BETA-ZEOLITES
Luisa Pasti‡, Elena Sarti‡,§, Alberto Cavazzini‡, Nicola Marchetti‡,§, Francesco Dondi‡,
Annalisa Martucci†
‡
Department of Chemistry and Pharmaceutical Sciences, University of Ferrara, Via L.
Borsari, 46, 44123 Ferrara, Italy
†
Physics and Earth Sciences Department, University of Ferrara, Via G. Saragat 1, 44121
Ferrara, Italy
§
Terra&AcquaTech Laboratory, University of Ferrara, Via Ercole I d’Este, 32, 44121
Ferrara, Italy
Contains:
Pages: 10
Tables: 3
Figures: 6
Contents:
1. Table S1. Molecular structure and physical chemical properties of the studied drugs.
2. Table S2. Zeolites characteristics.
3. Experimental: HPLC/MS
4. Experimental: HPLC/DAD and Table S3: Mobile phase composition
5. Adsorption Kinetics Experiments
6. Figure S1. Uptake of ATN, KTP and HCT on Beta360c vs. time.
7. X-Ray Diffraction: Experimental and Results
8. Figure S2. Observed powder diffraction patterns of a) as-synthesized and b) calcined
beta samples.
9. Figure S3. X-ray powders diffraction pattern collected on Beta25c before and after ATN
adsorption.
10. Figure S4: Adsorbed amount (q) vs. NaCl concentration of KTP, and ATN on Beta25c.
11. Figure S5: Adsorption isotherms in a low concentration range of KTP and on zeolite
Beta25.
12. Figure S6: K ads vs. K ow for ATN, HCT and KTP on Beta25c and Beta360c.
13. References
1. Table S1.
Molecular structure and physical chemical
properties of the studied drugs.
Water
Solubility
pKa
log Kow
Ketoprofen
(Non-steroidal antiinflammatory)
0.5 mg/ml
[39]
4.02
[40]
3.12
[41]
Atenolol
(β-blocker)
13.3 mg/ml
[41]
9.6
[41]
0.16-0.50
[41]
Hydrochlorothiazid
e
(Diuretic)
0.6-1
mg/ml [42]
pKa1=7.9
pKa2=9.2
[41]
-0.07
[41]
Analyte
Formula
2. Table S2. Zeolites characteristics.
Name
Zeolyst
SiO2/Al2O3 Mole
Nominal Cation
Surface Area
Products
Ratio
Form
(m2/g)
Beta25
CP814E
25
Ammonium
680
Beta38
CP814C
38
Ammonium
710
Beta360
CP811C-300
360
Hydrogen
620
3. HPLC/MS
HPLC/MS analyses were made by means of Surveyor micro-HPLC hyphenated to a
linear trap quadrupole (LTQ) mass spectrometer (LTQ XL Thermo Scientific, Waltham,
MA, USA). The HPLC apparatus was composed of a solvent delivery system, a quaternary
pump (including a membrane degasser) and an autosampler (including a thermostated
column compartment). The LTQ system was equipped with an electrospray ionization
(ESI) ion source. The mobile phase was obtained as a mixture of methanol:water:formic
acid 0.1% v/v. Chromatographic separation was performed under gradient elution
conditions where the methanol content varied from 10% to 95% in 10 minutes, then held
isocratically at 95% for 3 minutes before reconditioning the column. The flow rate was 200
µL/min, while the column was thermostated at 25 °C. The column was 50 x 2.1 mm
(Restek, Bellefonte, PA, USA) and packed with a C18 silica-based stationary phase with a
particle diameter of 3 µm [11]. The injection volume was 5 µL for all standards and
samples. MS experimental conditions were as follows: spray voltage 4 kV, capillary
temperature 350 °C, capillary voltage 29 V and tube lens 55 V for positive ESI conditions.
The data reproducibility calculated from three repeated independent solutions and
expressed as CV% was 3% for KTP and 4% for HTC.
4. HPLC/DAD
A HPLC/DAD (Waters, MA, USA pompa: Waters 515, DAD: Waters PDA 996) was
employed under isocratric elution conditions, reported in Tab. S3. The flow rate was 1
mL/min, while the column was thermostated at 25 °C. The column was 150 x 4.6 mm
(Phenomenex, CA, USA) and packed with a C18 silica-based stationary phase with a
particle diameter of 5 µm. The injection volume was 20 µL for all standards and samples.
Table S3. Mobile phase composition employed to analyze the three drugs.
% organic solvent
% phosphate
tR (min)
λ (nm)
buffer 2mM pH = 3
KTP
60 (methanol)
40
7.3
255
HCT
15 (methanol)
85
5.1
224
ATN
5 (acetonitrile)
95
8.3
225
5. Adsorption Kinetics Experiments
To estimate the equilibrium time, i.e. the time required to achieve equilibrium distribution of
the drugs between the two phases, the adsorption kinetics was investigated. The uptake
data obtained for the three pharmaceuticals (i.e. KTP, ATN, HCT) on Beta360c are shown
in Fig. S1.
6. Figure S1. Uptake of ATN (green squares), KTP (blue squares) and HCT (red squares)
on Beta360c vs. time.
16.0
Uptake (mg g-1)
14.0
12.0
10.0
8.0
6.0
KTP - Beta360c
4.0
HTC - Beta360c
2.0
ATN - Beta360c
0.0
0
20
40
60
time (min)
80
100
7. X-ray Diffraction.
Powder patterns of Beta samples were recorded on a Bruker D8 Advance Diffractometer
equipped with a Sol-X detector, using Cu Kα1, α2 radiation in the 3°-100° 2 θ range and a
counting time of 12 s/step . The same conditions were also maintained for X-ray collection
data on the beta samples after drugs adsorption.
Unit cell parameters were determined by the Le Bail method using the GSAS package [S1]
and the EXPGUI graphical interface [S2], starting from the unit cell parameters reported in
Refs. [22, 23]. The Bragg peak profile was modelled using a pseudo-Voigt peak-shape
function [S3] with 0.01% cut-off peak intensity. The background curve was fitted using a
Chebyschev polynomial with 20 variable coefficients. The 2θ-zero shift was accurately
refined into the data set pattern. The scale factor and unit-cell parameters were allowed to
vary in all the cycles.
A careful examination of the as-synthesized sample diffraction patterns (see Fig. S2a)
clearly reveals differences in both the intensity and the position (i.e., 2θ angle) of
diffraction peaks. The former depends on type and atomic parameters, such as positional
coordinates x, y, z, isotropic temperature factors, etc.; the latter is a function of the unit cell
parameter values. The differences are particularly important in the low angle region, as
they indicate disorder and/or changes in the extraframework region. The 2θ region
included between 17-35° (see Fig. S2a) shows a peak broadening for Beta360, higher
than that for Beta25 and Beta38, due to different crystallite size and/or to different fractions
of the polytypes A and B in the samples. This result suggests Beta360 to be more
defective than the other two BEAs, possibly due to the dealumination process carried out
to increase the SAR of this materials.
The X-ray diffractograms of calcined samples are still characteristic of well crystallized
beta (Fig. S2b).
To clarify the role played by the different surface area of Beta360 e Beta25, X-ray
diffraction patterns were collected for the zeolites before and after adsorption of the
selected drug (ATN). In fact, differences in terms of both intensity and position of the
diffraction peaks can give indication regarding incorporation of host molecules inside the
porous structure of zeolites. As an example, the X-ray powder diffraction pattern for the
system ATN-Beta25c is reported in Fig. S3. The strong differences of the diffraction peaks
with respect to Beta25c both in terms of intensity and position and as variations in unit cell
parameters (Table 1 main text) give evidence of the effective incorporation of ATN inside
the pores of the zeolite.
8. Figure S2: a) Observed powder diffraction patterns of as-synthesized beta samples,
showing the differences both in the intensity and position of the diffraction peaks. The
insert higlights the peak broadening in Beta360. b) Observed powder diffraction patterns of
calcined Beta25, Beta38 and Beta360
a)
Beta25
Beta38
Beta360
b)
Beta25c
Beta38c
Beta360c
9. Figure S3: X-ray powders diffraction pattern collected on Beta25c before (blue) and
after ATN adsorption (black).
10. Figure S4: Adsorbed amount (q) vs. NaCl concentration of KTP, and ATN on Beta25c
(circles)
q (mg g-1)
190
KTP
170
ATN
150
130
110
90
70
50
0
0.02
0.04
0.06
0.08
0.1
0.12
[NaCl] mol L-1
11. Figure S5. Adsorption isotherms in a low concentration range of a) KTP (blue
symbols) and b) HCT (red symbols), on zeolite Beta25.
2.5
q (mg g-1)
2
y = 33.2x - 0.02
R 2 = 0.9939
1.5
y = 28.7x - 0.04
R 2 = 0.9979
1
HTC - Beta25
KTP - Beta25
0.5
0
0
0.01
0.02
0.03
0.04
0.05
Ce (mg
0.06
0.07
L-1)
12. Figure S6: K ads vs. K ow for ATN (green symbols), HCT (red symbols) and KTP (blue
symbols) on Beta25c (circle) and Beta360c (square).
Kads
1000
800
600
400
200
0
0.1
10
100
1000
10000
-200
Kow
13. References
[S1] Larson, A. C., Von Dreele, R. B., Los Alamos National Laboratory Report LAUR,
2000, 86.
[S2] Toby, B. H., J. Appl. Cryst. 2001, 34, 210-213.
[S3] Thompson, P., Cox, D. E., Hastings, J. B., J. Appl. Crystallogr. 1987, 20, 217-236.