Supplementary information
Cyclodextrin-crosslinked poly(acrylic acid): Adhesion and controlled release of
diflunisal and fluconazole from solid dosage forms
Marguerite J. Kutyła,*,1 Michael W. Boehm,2 Jason R. Stokes,2 P. Nicholas Shaw,1 Nigel M.
Davies,1 Ross P. McGeary,1,3 Jonathan Tuke4 and Benjamin P. Ross*,1
1
The University of Queensland, School of Pharmacy, Qld 4072, Australia
The University of Queensland, School of Chemical Engineering, Qld 4072, Australia
3
The University of Queensland, School of Chemistry and Molecular Biosciences, Qld 4072,
Australia
4
School of Mathematical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
2
*Corresponding authors. Mailing address: The University of Queensland, School of
Pharmacy, Brisbane, Qld 4072, Australia. Phone: +61 7 33461900. Fax: +61 7 33461999. Email: m.kutyla@uqconnect.edu.au (M.J.K.), b.ross1@ uq.edu.au (B.P.R.).
S1
Weight and thickness uniformity
Mean thickness, measured with digital calipers (accuracy of 0.01 mm) and mean tablet
mass, measured using a four-figure analytical balance, were determined for five tablets from
each formulation.
The tablets made of polymer only were thinner than the corresponding physically mixed
polymer/drug tablets (Table S1). A one-way ANOVA test indicated that the different
formulations of Carbopol were statistically different in thickness from each other at a
confidence level of p < 0.05, as were the βCD-PAA tablets, but no significant difference was
found between the HPβCD-PAA tablets. The physically mixed polymers with either
fluconazole or diflunisal were thicker than those of the complexed diflunisal. Visual
inspection of the lyophilized pre-complexed conjugates revealed fluffier powders than the
corresponding physically mixed conjugates thus the differences in morphology of the
material may be responsible for the altered properties observed, as reflected in the literature
(1-4). A certain proportion of the drug is also located in the cavity of the CD thus essentially
removing it from the bulk volume of the polymer, as well as expected to be molecularly
dispersed throughout the polymer, thus not affecting compressibility of the original polymer.
Table S1 Uniformity of tablets (n = 5)
Tablets
CBPL
CBPL & DIF phys
CBPL & FLZ phys
βCD-PAA polymer
βCD-PAA & DIF cplx
βCD-PAA & DIF phys
βCD-PAA & FLZ phys
HPβCD-PAA polymer
HPβCD-PAA & DIF cplx
HPβCD-PAA & DIF phys
HPβCD-PAA & FLZ phys
Weight ± SD (mg)
99.6 ± 3.0
97.8 ± 5.2
98.3 ± 1.6
99.1 ± 2.1
97.3 ± 1.3
100.1 ± 1.8
99.7 ± 4.8
98.8 ± 2.3
100.4 ± 2.0
99.8 ± 2.1
100.3 ± 4.9
Thickness ± SD (mm)
1.17 ± 0.02
1.24 ± 0.03
1.20 ± 0.01
1.21 ± 0.02
1.21 ± 0.02
1.24 ± 0.03
1.28 ± 0.04
1.25 ± 0.03
1.25 ± 0.05
1.29 ± 0.04
1.27 ± 0.05
CBPL – Carbopol, DIF – diflunisal, FLZ – fluconazole, phys – physical mixture; cplx –
complex.
S2
Release of βCD from PAA tablets
% cumulative release
100
80
60
40
CD cplx
CD phys
DIF cplx
DIF phys
20
0
0
50
100
150
200
time (min)
Figure S1 Release of βCD and diflunisal from tablets made of physical mixture of PAA and
βCD, with either physically mixed of pre-complexed drug (each point and error bar
represents the mean ± SD of three experiments).
Swelling indexes of tablets
60
50
SI
40
30
20
CBPL FLZ
CBPL DIF
CBPL
10
0
0
200
400
600
800 1200
time (min)
Figure S2 Swelling indexes of different Carbopol tablet formulations (each point and error
bar represents the mean ± SD of three experiments).
S3
SI
30
20
HPCD-PAA
CD-PAA DIF cplx
CD-PAA
HPCD-PAA DIF cplx
10
0
0
200
400
600
800 1200
time (min)
Figure S3 Swelling indexes of different HPβCD-PAA and βCD-PAA tablets (each point and
error bar represents the mean ± SD of three experiments).
PAA & DIF
PAA + CD & DIF phys
PAA + CD & DIF cplx
SI
3
2
1
0
0
50
100
150
200
time (min)
Figure S4 Swelling indexes of different PAA tablet formulations (each point and error bar
represents the mean ± SD of three experiments).
S4
PDMS disc
Figure S5 35mm diameter custom attachment for Haake MARS III rheometer with cured-inplace PDMS
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