Effect of solid dispersions and physical mixtures of ibuprofen with Pluronic F-127 and PEG 1000 on the in vitro drug release from ibuprofen-adhesive layers

The transdermal delivery of drugs can be enhanced by suppressing their melting point
(Kasting et al 1987). In this work we examined this theory on the in vitro drug release
from drug-in-adhesive layers. Ibuprofen (m.p. = 73.5–76.3°C) was used as model
drug together with Pluronic F127 (m.p. = 54.4–60.5°C) and PEG 1000 (m.p. = 37–
40.9°C). Solid dispersions were prepared with ibuprofen:polymer ratios ranging from
90:10 to 10:90 according to the fusion method and were allowed to solidify at 20°C in
a lightproof desiccator for a week. The melting temperature range of the solid dispersions, ibuprofen, Pluronic F127 and PEG 1000 was then recorded (n = 3) using a hot
stage microscope at a heating rate of 3°C/min and phase diagrams were constructed.
The eutectic compositions were identified as 30:70 ibuprofen:Pluronic F127 and
15:85 ibuprofen:PEG 1000 at 43.45 ± 2.5°C and 29.6 ± 1.2°C, respectively. The following binary mixtures of ibuprofen:polymer were prepared as solid physical mixtures (PM) and solid dispersions (SD); 60:40, 40:60, 30:70 with Pluronic F127 and
60:40, 30:70, 25:75, 20:80 with PEG 1000. Each binary mixture was added into the
required amount of liquid acrylic adhesive to produce dried circular adhesive layers
with a target ibuprofen loading of 0.05 g and ibuprofen concentration of 10% w/w.
Ibuprofen-adhesive layers without polymer were also prepared by mixing either solid
or molten ibuprofen with the acrylic adhesive. All layers had a mean surface area of
4.5 ± 0.35 cm2
. The drug release of ibuprofen from each set of layers (n = 3) was
tested over 5 h in a paddle dissolution apparatus using citrophosphate buffer
(pH = 5.6) under sink conditions, at 32°C. The UV analysis was carried out at 272 nm.
The cumulative ibuprofen release values (mgcm−2
) at 5 h were: 7.44 ± 0.5 (40:60) >
2.98 ± 0.5 (60:40) > 1.7 ± 0.15 (30:70) from the SD-adhesive layers with Pluronic
F127; 5.81 ± 0.25 (30:70) > 5.4 ± 0.6 (25:75) > 4.5 ± 0.6 (20:80) > 2.4 ± 0.1 (60:40)
from the SD-adhesive layers with PEG 1000; 4.44 ± 0.5 (40:60) > 2.65 ± 0.4 (60:40) >
1.3 ± 0.9 (30:70) from the PM-adhesive layers with Pluronic F127; 4.66 ± 0.7 (30:70)
> 3.7 ± 0.5 (25:75) > 3.1 ± 0.3 (20:80) > 1.89 ± 0.1 (60:40) from the PM-adhesive layers with PEG 1000; 1.85 ± 0.04 and 1.55 ± 0.3 when molten and solid ibuprofen were
used, respectively. Ibuprofen release did not improve using the eutectic composition
with Pluronic F127, possibly due to increased ibuprofen solubilisation in the adhesive
and subsequent decrease in the thermodynamic activity of the formulation. A significant increase in ibuprofen release (t-tests, P < 0.05) was shown for the compositions
adjacent to the eutectic one, with Pluronic F127 (40:60) and PEG 1000 (20:80, 25:75,
30:70), from both SD- and PM-adhesive formulations, compared to the ibuprofenadhesive formulations. Additional studies using different drugs will further examine
the described findings.