Purpose: Transdermal drug-in-adhesive patches provide a controlled drug release across skin and are prepared by dispersing the drug in pressure sensitive adhesives (PSAs). In addition to the drug, PSAs form a vital component of transdermal patches, that directly affect the release and performance characteristics of the system. The aim of this study was to design and characterize transdermal patches formulated using drug loaded in different PSAs, including acrylate, polyisobutylene (PIB), and silicone. The patches prepared were evaluated for their permeation, release profile and adhesive properties.
Methods: Lidocaine (MW=234.3 g/mol, LogP=2.4) was chosen as a model drug to study the effect of matrices on patch performance. Patches were prepared employing adhesives: Acrylates copolymer (DURO-TAK 87-2287), PIB (DURO-TAK 87-6908), and Silicone Dow Corning® BIO-PSA 7-4301. The saturation points were determined for each matrix by performing patch crystallization studies. Transdermal patches (100 gsm) were prepared by casting the wet drug-in-adhesive blends containing lidocaine at its saturation points on 3M Scotchpak™1022 release liners, followed by drying at 75 ̊C for 20 min and lamination on 3M Scotchpak™ 9733 as the backing membrane. Patches were further tested for tack, shear and peel properties. In vitro release studies were carried out according to USP guidelines using a Sotax AT 7smart Dissolution Tester. USP apparatus 5 (the paddle over disk method with a watch glass–patch–screen sandwich assembly) was used with phosphate-buffered saline pH 7.4 as the medium and paddle speed was set to 50 rpm. Aliquots were withdrawn over 72 hours and filtered through 0.45µm filter syringes prior to HPLC-UV analysis. Skin permeation study was performed using dermatomed porcine ear skin mounted on a vertical Franz diffusion cell for each patch (n=4). Sampling of receptor solution was performed at pre-determined time points over 72 hours and analyzed for drug content using HPLC. Statistical analysis was performed using one-way ANOVA and p<0.05 was considered to conclude significant difference between the test groups.
Results: Patch crystallization studies revealed the saturation points of lidocaine in silicone, PIB and acrylate patches to be 2.50, 3.50, and 25.00% (w/w) respectively. The percentage of lidocaine released as a function of time is shown in Fig. 1. Silicone adhesive demonstrated rapid release of the drug with significantly higher release within one hour of the study (25.23±7.57), compared to acrylate (6.06±2.17) and PIB (5.63±1.07). The total percentage released at the end of 72 h for silicone, PIB, and acrylate was 83.21±3.35, 55.36±2.39, and 39.58±3.60% respectively. However, in the in vitro studies, the cumulative amount permeated from acrylate was significantly higher than silicone and PIB at the end of the study, though no difference was observed in the first hour between the three adhesives. The cumulative amount of lidocaine permeated in 72 hours was 352.92±63.37, 402.89±16.30, and 2575.91±322.14 µg/sq. cm for silicone, PIB, and acrylate patches, respectively. The permeation flux was calculated to be 55.07, 28.94, and 11.94 µg/cm2/h, respectively. The permeation profile of lidocaine from the different patches has been illustrated in Fig. 2. Shear evaluation of the patches revealed 16.88±3.31, 2.38±0.41, and 0.1±0.00 min for silicone, PIB, and acrylate respectively, as the time required to skid the patches adhered to stainless plates with a 1000 g force. In the 180° peel adhesion test, the force required to peel the patch from stainless steel panel was measured to be 235.55±35.54, 3.80±1.55, 233.83±35.86 g respectively. Although acrylate showed lower shear properties and a low force was required to peel the PIB patch, the patches showed comparable tack properties with absolute positive forces of 480.33±65.12, 379.70±136.09, and 280.60±86.80 g for the silicone, PIB, and acrylate adhesives.
Conclusion: Lidocaine patches with saturation solubility in silicone, PIB and acrylate adhesives were successfully prepared and evaluated for permeation, release and adhesion properties. Although all the patches were prepared at saturation solubility, the choice of PSA affected the drug release and permeation profile. The acrylate patches contained ten times higher drug amount than silicone patches, but the amount of drug permeated was only two folds higher. In addition, results indicate that the release of drug does not linearly correlate to saturation, as the silicone patches comprising of the lowest amount of drug loading, showed the highest percentage release.
Ajay Banga– Professor and Department Chair, Mercer University, Atlanga, Georgia