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10-2
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700
600
500
400
300
200
100
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300
250
200
150
100
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CÉLULAS ENCAPSULADAS
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0
100
200
300
400
500
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0
100
200
300
400
500
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El presente estudio tiene por objeto
caracterizar la disposición de vancomicina en
pulmón cuando se administra en forma de
liposomas por vía pulmonar.
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3.0e-7
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2.0e-7
1.5e-7
1.0e-7
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LY
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1.8e-7
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1.6e-7
TC7/Caco-2
1.4e-7
1.2e-7
1.0e-7
8.0e-8
6.0e-8
4.0e-8
2.0e-8
0.0
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de confianza del 95% bootstrap para los parámetros
cinéticos y el plazo de validez.
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0
2
10000
35
8000
2
4
4
4.0
3.9
2
0
Theoretical Quantiles
3.8
3.7
Sample Quantiles
3.4
-2
3.5
500
-4
3.6
Frequency
26000
22000
S a m p le Q u a n tile s
4
18000
1000
2
2000
0
Theoretical Quantiles
500
0
Normal Q-Q Plot
1500
-2
1000
-4
Normal Q-Q Plot
Ea
-2
Theoretical Quantiles
30
35
Ln A
18000 20000 22000 24000 26000 28000
-4
Histogram of t90%
Histogram of Ea
10000
t90%
0
30
6000
25
S a m p le Q u a n tile s
1500
F requenc y
500
2000
0
25
0
F requenc y
20
6000
Sample Quantiles
4
0
Theoretical Quantiles
Normal Q-Q Plot
2000
-4
Co, %
Histogram of Ln A
4000
500
1000
Frequency
9 9 .8
9 9 .4
S a m p le Q u a n tile s
9 9 .0
2000
1000
98.8 99.0 99.2 99.4 99.6 99.8 100.0
Normal Q-Q Plot
2000
Histogram of t90%
Normal Q-Q Plot
0
F re qu enc y
Histogram of Co, %
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t90%
3.8
4.0
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0
2
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4
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Results and discussion
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Homogeneous, flexible and transparent
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films were obtained from the prepared
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solutions. All films were easily removed
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from the cast plate and no pores or cracks
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were detected. Thickness of films varied
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from 92.7 ± 8.9 (Film I) to 95.3 ± 9.1 (Film
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II) to 99.5 ± 10.2 μm (Film III).
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Errors bars represent standard deviations
based on four experiments.
10
Viscosity (Pas)
Fim I
Film II
Film III
Conclusions
HA/HPMC films showed the capability to
control diclofenac transcorneal permeation
rate in vitro. Moreover, the drug
permeation rate was affected by the HA
concentration in the film: the higher the
concentration the slower the permeation.
Therefore, these preliminary results
indicate that HA/HPMC in appropriate ratio
can be used as drug controlled delivery
systems for topical ocular administration.
1
0.1
0.01
1
10
100
1000
Shear rate (s-1)
Fig. 1. Effect of shear rate on shear
viscosity of HA/HPMC films.
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The flow curves, which show viscosity as
a function of the shear rate, are reported
in Fig.1 for the three studied formulations.
The viscosity decreased by increasing the
shear rate, that is, these systems showed
a shear thinning or a pseudoplastic
behaviour. The Films I presents ηo values
(0.165±0.001) lower than the Film II
(0.556±0.003) and Film III (0.981±0.006).
Therefore, the viscosity increased as a
function of the HA amount.
The transcorneal permeation profiles of
diclofenac are shown in Fig. 2. Results
indicate that the Film I presented the
highest drug penetration rate across the
cornea and that the incorporation of
growing quantities of HA into the film
systems reduced the drug permeation
capacity. Permeation coefficient values
calculated for each formulation confirmed
these results: Film I (0.271±0.014), Film II
(0.119±0.003) and Film III (0.033±0.003).
These results could be explained as the
consequence of the increased film
viscosity as HA concentration increased.
Film I
Film II
Film III
-2
-1
Cumulative amount (mg.cm .h )
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0
2
4
6
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HDQVRUHQD#XQDYHV
8
Time (h)
Fig. 2. Permeation of diclofenac through
excised cornea from the bovine eye.
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1,000
Trehalose_5% Trehalose_10% Trehalose_15%
900,0
800,0
700,0
600,0
500,0
400,0
300,0
200,0
100,0
0,0
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Sucrose
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80
100
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80
100
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100
150
200
250
300
350
400
40
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60
60
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20
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TLE negativo con sumatriptan
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0
40
TLE negativo 50:40:10
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40
20
60
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31P NMR a 303 K
100
80
60
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31P NMR a 303 K
450
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100
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100
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60
40
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31P NMR a 338 K
500
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100
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47
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