Evaluation of the effect of ibuprofen crystallisation on its release from silicone and acrylic ibuprofen-adhesive layers

Maximum drug release from transdermal patches is achieved when the formulation
is at its maximum thermodynamic state. The attainment of such a state can be problematic when the drug is prone to crystallisation (Kim & Choi 2002). In this work,
ibuprofen, a weakly acidic compound (pKa = 4.8) with low aqueous solubility, was
used as the model drug together with two silicone (silicone-1, silicone-2) and an
acrylic polymer adhesives. The saturation solubility of ibuprofen in each of the
adhesives was examined by mixing ibuprofen in increasing amounts with the liquid
adhesives and then examining the dried mixtures for undissolved drug and crystal
formation over a period of one week, using a polarised light microscope. The saturation concentration of ibuprofen was found to be 6.5 ± 0.5% w/w in silicone-1 and
5 ± 0.5% w/w in silicone-2. In the acrylic adhesive there was an initial crystal
formation of ibuprofen at concentrations between 13 and 15% w/w. Circular ibuprofen-adhesive layers (mean surface area of 9.5 ± 0.5 cm2
) on a fluoropolymer
liner were prepared, containing ibuprofen in a near-saturation concentration
(6.5 ± 0.7% w/w, 5 ± 0.4% w/w, 13 ± 0.5% w/w) and then in a supersaturated concentration (16.5 ± 0.5% w/w, 14 ± 1% w/w, 22.5 ± 0.5% w/w) with silicone-1, silicone-2 and the acrylic adhesive, respectively. The supersaturated layers with the
silicone adhesives showed white ibuprofen crystals under the microscope, in contrast to the acrylic layers, which turned clear on storage. Each set of drug-adhesive
layers (n = 4) were tested for their drug release profile over 7 h in a paddle dissolution apparatus using citrophosphate buffer (pH = 5.6) as the dissolution medium
under sink conditions, at 32°C. The UV analysis was carried out at 272 nm. The
mean cumulative ibuprofen release (mg/cm2
) at 7 h was 0.62 ± 0.2, 0.5 ± 0.2 and
0.57 ± 0.16 from the near-saturated layers; 0.68 ± 0.07, 0.49 ± 0.1 and 1.7 ± 0.11
from the supersaturated layers, with silicone-1, silicone-2 and acrylic adhesive,
respectively. All sets of layers showed biphasic drug release, with a second burst
after 2–4 h. The non-significant change of ibuprofen release from the silicone-1
(t-test, P = 0.879) and silicone-2 (t-test, P = 0.227) between near-saturated and
supersaturated formulations agree with previous studies where the presence of ibuprofen crystals suppressed further drug release from supersaturated silicone formulations (Cilurzo et al 2005). The absence of ibuprofen crystals even at high loadings
(> 22% w/w) in the acrylic adhesive, without the addition of crystallisation inhibitors, and the significantly higher (P = 0.001) ibuprofen release from the clear concentrated ibuprofen-acrylic formulations, render acrylic-based adhesives good
candidates for further studies on the formulation of drug-in-adhesive layers with
ibuprofen.