Design of SEBS-based pressure-sensitive adhesives for medicated plasters preparation

INTRODUCTION Styrene-block-(ethylene-co-butylene)-block-styrene (SEBS) copolymers are well known biocompatible elastomers with outstanding stability under physiological conditions1. It was also demonstrated that the compounding with paraffin oil and aliphatic resins (tackifier) allows to obtain a pressure sensitive adhesive (PSA) with a very high creep resistance2. These features make SEBS a potential candidate for the design of transdermal patches and/or medicated plasters. In this work the influence of SEBS molecular weight and tackifier type on the adhesive properties, mechanical characteristics and biopharmaceutical performances of medicated plasters containing S-ibuprofen (S-IB) were investigated. EXPERIMENTAL METHODS Materials Three types of SEBS were kindly donated by Polimeri Europa (San Donato Milanese, Milan, Italy). They were SOL TH® 2311 (Mw = 45.61 kDa), SOL TH® 2312 (Mw = 64.23 kDa) and SOL TH® 2315 (Mw = 176.35 kDa). The aliphatic hydrocarbon resins Regalite R1100® and Eastotac H100W® were used as tackifiers and they were received as a gift from Eingemann & Veronelli Spa (Rho, Milan, Italy). Mixtures preparation To prepare the polymeric solution, all components were dissolved in toluene. The final composition of the placebo PSAs is illustrated in Table 1. For the preparation of the drug-loaded mixtures, S-IB was added at 10% (w/w). Rheological characterization The rheological properties were obtained by using a rotational rheometer (Discovery Hybrid Rheometer). A frequency-sweep deformation was applied into the samples and the response in terms of stress was measured. Probe tack test The adhesion and debonding mechanisms of the placebo PSAs on a stainless steel probe were determined by using a custom-designed probe tack tester. Tack experiments were performed at 25 °C and 32 °C with a compression force of 30 N; the contact time was set at 10 s and the debonding velocity was varied from 10 to 1000 μm/s. PSA thickness was about 200 ± 10 μm. Drug release rate S-IB plasters were prepared by using a LabCoater unit Mathis LTE-S(M). Final thickness of adhesive matrices was about 55 ± 5 μm. The S-IB release was carried out using a USP28 paddle dissolution apparatus (8.034 cm2; 300 mL; pH 7.4 phosphate buffer; 32 ± 1 °C; 25 rpm). RESULTS AND DISCUSSION Rheological characterization In order to develop suitable medicated plasters, a balance between peel and creep is crucial3. Therefore, the PSA should have viscoelastic behaviour: in fact, as a viscous liquid it should be able to dissipate energy during the peel process (at high shear rate), while as a solid it should have a good resistance to shear over long time4. The rheological measurements showed as the PSAs made with SEBS-low molecular weight behaved as viscoelastic fluids over the whole range of frequencies, while PSAs made with the intermediate and the high molecular weight polymers behaved more like moderately viscoelastic solids. As shown in Fig. 1, only for the formulation containing SOL THÒ 2311 (Form.1) the elastic modulus decreased strongly at low frequency, typical of a material with a pronounced viscoelastic character. No differences on the rheological pattern were observed by changing the tackifier. The probe tack test is generally used to evaluate the instant adhesion properties of a PSA, but the debonding phase can be also studied to analyze the failure mechanism. Form. 1-6 showed a liquid-like behaviour at the lower debonding velocity with many digitations, because they have more time to relax (Fig. 2, black line). On the contrary, at the faster debonding velocity, they did not have time to relax: in these conditions, PSAs showed a more solid-like behavior and the formation of a high number of cavities was observed (Fig. 2, red line). Considering that in the normal usage conditions a plaster must adhere to the skin for a long time, the studied PSAs will have time for relaxation, showing in the debonding phase an interfacial behaviour. The adhesive behaviour as well as the shape of the stress-strain curve and the debonding mechanisms did not qualitatively change with polymer molecular weight at all the debondig rate tested. There was no relationship between the maximum stress values measured in probe tack test at 10, 100 and 1000 μm/s debonding velocity and the elastic modulus of the polymer measured at a frequency ranging between 0.01-100 rad/s and a strain of 0.1%. The most important results shown in Fig. 3a concern the increase in the maximum strain and adhesion energy with the SEBS molecular weight. Figure 3a refers to the formulations prepared with Regalite H1100 for sake of clarity since tackifier did not influence PSA characteristics as demonstrated in Figure 3b. Drug release The percentage of S-IB released from the prepared plasters (Fig. 4) was not influenced by SEBS molecular weight and the profiles were superimposable. The drug release was completed within 24 hours and it followed Higuchi pattern. CONCLUSIONS Overall data allowed to demonstrate the feasibility to design transdermal patches and/or medicated plasters made of SEBS. The resin type used in the preparation of SEBS-based PSA did not influence matrix behavior. SEBS-low molecular weight is the polymer worthy of consideration to design a medicated plaster because of its favorable viscoelastic behaviour. REFERENCES 1. Hou J. et al. ACS Appl. Mater. Interfaces. 6 (2014). 2. Pagani S. et al. Patent Number US20110243985 A1 (2009). 3. Cilurzo F. et al. Exper Opin. Drug Deliv. 11, 1033-1045 (2014). 4. Deplace F. et al. The Journal of Adhesion. 85, 18-54 (2009).