INFLUENCE OF MCM-41 PARTICLES
MORPHOLOGY AND FUNCTIONALIZATION ON
IBUPROFEN UPTAKE AND RELEASE
Valentina Aina
1.
2.
3.
4.
V. Aina, G. Cerrato, G. Magnacca, C. Morterra
Dip. Chimica IFM, Università di Torino, Torino-Italy
V. Cauda, B. Onida, E. Garrone
Dip. di Scienza dei Materiali e Ingegneria Chimica Politecnico di Torino, Torino-Italy
F. Balas, M. Colilla, M. Manzano, M. Vallet-Regì
Dpto. de Quimica Inorganica y Bioinorganica Universidad Complutense de Madrid, Madrid-Spain
M. Rodriguez, C. Otero
Dpto de Quimica, Universidad de las Islas Baleares, Palma de Mallorca-Spain
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Ordered mesoporous silica: MCM-41
Si
Si
Si
OH
OH
OH
Ordered mesoporous silica
allow to adsorb and deliver a
drug in a homogeneous and
controlled way
 Particles morphology influence for drug release
Irregular particles
Spherical particles
 Functionalization influence for drug release
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Name samples
Description
MCM-41 irr
MCM-41 particles of irregular shape
MCM-41 sph. 490 nm
MCM-41 particles of spherical shape, with dimension of 490 nm
MCM-41 sph. 615 nm
MCM-41 particles of spherical shape, with dimension of 615 nm
MCM-41 sph. 770 nm
MCM-41 particles of spherical shape, with dimension of 770 nm
SEM
Irregulares particles
(a)
(b)
(c)
Sphericals particles
2 m
490 nm
2 m
615 nm
2 m
770 nm
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Samples characterization
Samples
Dp
(nm)
Vp
(cm3/g)
SBET
(m2/g)
MCM-41 IRR
3,4
0,80
928
(100)
2,30
Intensity
20000
10000
(110)
3,96 (200)
4,48
3000
(100)
2,44
2000
Samples
Dp
(nm)
Vp
(cm3/g)
SBET
(m2/g)
MCM-41 sph 490nm
2,1
0,46
874
MCM-41 sph 615nm
1,78
0,48
1078
MCM-41 sph 770nm
1,95
0,58
1198
Intensity
MCM-41 Irregular
30000
MCM-41 spherical 490 nm
MCM-41 spherical 615 nm
MCM-41 spherical 770 nm
1000
0
0
2
4
6
8
10
2
4
2 (degree)
30
8
10
20
MCM-41 spherical 490 nm
MCM-41 spherical 615 nm
MCM-41 spherical 770 nm
20
5
dV/dlogD
4
10
3
2
1
0
0
10
20
30
40
3
10
2
dV/dlogD
Quantity Adsorbed (mmol/g)
MCM-41 Irregular
Quantity Adsorbed (mmol/g)
6
2 (degree)
0
50
Pore Width (A)
0
0,0
0,2
0,4
0,6
Relative Pressure (p/p0)
0,8
1,0
1
0
10
20
30
40
Pore Width (A)
0
0,0
0,2
0,4
0,6
Relative Pressure (p/p0)
0,8
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
1,0
50
Ibuprofen Uptake
[drug]mesoporous  [drug]solvent
mesoporous
material
drug solution
Uptake conditions:
 mg ibuprofen/ mg material = 1
 Solution of ibuprofen with n-pentane (33 mg/ml)
 24h with stirring (two methods):
- magnetic stirring
- orbital stirring
Magnetic stirring
Orbital stirring
Samples
% ibuprofen
(TGA/DTA)
MCM-41 Irr+ Ibu
26%
Samples
% ibuprofen
(TGA/DTA)
MCM-41 sph 490 nm + Ibu
26%
MCM-41 Irr+ Ibu
21%
MCM-41 sph 615 nm + Ibu
25%
MCM-41 sph 490 nm + Ibu
11%
MCM-41 sph 770 nm + Ibu
25%
MCM-41 sph 615 nm + Ibu
15%
MCM-41 sph 770 nm + Ibu
17%
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
5
MCM-41 irregular
MCM-41 irregular + ibuprofen
MCM-41 irregular after ibuprofen release
4
dV/dlogD
3
2
1
20
0
0
10
20
30
40
50
Pore Width (A)
2.5 nm
10
MCM-41 Irregular
MCM-41 Irregular + ibuprofen
MCM-41 Irregular after ibuprofen release
30000
(100)
2,30
0
0.0
0.2
0.4
0.6
0.8
1.0
20000
Relative Pressure (p/p0)
Samples
Dp
(nm)
Vp
(cm3/g)
SBET
(m2/g)
MCM-41 IRR
3,4
0,80
928
MCM-41 IRR + Ibu
2,5
0,32
514
MCM-41 IRR after release ibu
/
0,33
134
(100)
2,30
Intensity
Quantity Adsorbed (mmol/g)
30
10000
(110)
(200)
0
2
4
6
8
10
2 (degree)
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Ibuprofen release
mesoporous material
+
drug
SBF solution
Release conditions





Samples
Simulated biological fluids (SBF) at 37ºC and pH 7,4
Continuos stirring
50 mg of samples with 14 ml of SBF
Ibuprofen released monitored with UV-Vis
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Ibuprofen release
100
90
% ibuprofen released
% ibuprofen released
80
60
40
MCM-41 irregular
MCM-41 spherical 770 nm
MCM-41 spherical 615 nm
MCM-41 spherical 490 nm
20
80
70
0
0
100
200
300
Time (h)





400
500
600
0
100
200
300
400
500
600
Time (h)
Release fast
80% of ibuprofen released during the first 9 hours
15% of ibuprofen released more slowly
Spherical particles release the drug more slowly then irregular particles
Smaller are the spherical particles, slower is the ibuprofen release
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Functionalized mesoporous materials
The aim is to integrate organic groups onto the
pores surface through Si-C covalent bonds,
oriented towards the inner axes of the channels.
R
Requisites
 High degree of functionalization
 Homogeneous distribution throughout the pores surface
 To preserve the mesoporous structural arrangement due to its significance
in future applications
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Functionalization vs ibuprofen interaction
OH
OH HO
Si
Si
OSi
OH
Si
SiO
Cl
OH
Cl
NH2
Si OSi
Si
Si
SiO
Si
SiO
Si
HO
NH2
SiO Si
OSi
SiO
OSi
SiO
MCM-41 functionalization with AP-TES:
to investigate the effects towards
ibuprofen storage and release
OSi
OSi
.
SiO
OSi
Amount of AP-TES
Samples
% func.
(TGA/DTA)
Samples
%C
%H
%N
MCM-41 Irregular Fun.
13%
MCM-41 Irregular Fun
9,91
2,75
3,26
MCM-41 spher 490 nm + Fun
12%
MCM-41 spher 490 nm + Fun
8,46
2,38
2,76
MCM-41 spher 615 nm + Fun
13%
MCM-41 spher 615 nm + Fun
9,52
2,74
3,04
MCM-41 spher 770 nm + Fun
13%
MCM-41 spher 770 nm+ Fun
9,28
2,61
2,97
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
5
Samples characterization
3
2
MCM-41 irregular
MCM-41 irregular fun
MCM-41 irregular fun + ibuprofen
MCM-41 irregular fun after ibuprofen release
30000
1
0
10
20
30
40
50
30
Pore Width (A)
MCM-41 irregular
MCM-41 irregular fun
MCM-41 irregular fun + ibuprofen
MCM-41 irregular fun after ibuprofen release
(100)
2,26
20
(100)
2,32
20000
10
Intensity
0
Quantity Adsorbed (mmol/g)
dV/dlogD
4
(100)
2,28
0
0.0
0.2
0.4
0.6
0.8
1.0
10000
Relative Pressure (p/p0)
Samples
Dp
(nm)
Vp
(cm3/g)
SBET
(m2/g)
MCM-41 IRR
3,4
0,80
928
MCM-41 IRR + fun.
2,69
0,23
341
MCM-41 IRR + fun + ibu
-
0,05
30
0
2
MCM-41 IRR + fun after ibu rel
-
0,24
122
4
6
2 (degree)
8
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
10
Ibuprofen release
100
100
60
80
% ibuprofen release
% ibuprofen release
80
40
MCM-41 Irregular fun
MCM-41 sph 770 nm fun
MCM-41 sfh 615 nm fun
MCM-41 sph 490 nm fun
20
60
40
20
0
0
200
400
600
800
0
0
Time (h)
8
16
Time (h)
 After the functionalization the release profile is slower for all the samples
 After 9 hours the 50% of drug was released
 It can be clearly seen that spherical particles release more slowly than
irregular particles
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
24
Conclusions
IBUPROFEN UPTAKE
•
The ibuprofen uptake is the same in all samples with magnetic stirring.
•
It can be seen the influence of particles morphology in the uptake with orbital stirring.
•
The amount of ibuprofen uptake is slower with orbital stirring than magnetic stirring,
in the same conditions.
IBUPROFEN RELEASE
•
Spherical particles release the drug more slowly then irregular particles.
•
Smaller are the spherical particles, slower is the ibuprofen release.
•
After the functionalization the release profile is slower for all the samples.
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007
Acknowledgements
Research funded by MIUR (Project COFIN2006, Prot.
2006032335, Area 03 ), Consortium INSTM and Center of
Excellence for Nanostructured Interfaces and Surfaces
(University of Torino, Italy).
VI Convegno Nazionale sulla Scienza e Tecnologia dei Materiali. Perugia 12-15 giugno 2007