The effects of drug solubility parameter and concentration on the rheological properties and adhesive performance of drug-in-adhesive transdermal patches

Objectives To study the effects of drug solubility parameter and concentration on the rheological properties and adhesive performance of acrylic pressure-sensitive adhesive (PSA) transdermal patches. Methods Drug-in-adhesive patches were made by incorporating model drugs into acrylic PSA (DuroTak 87–900A, National Starch and Chemical, NJ, USA)transdermal patches. The six model drugs employed, together with their total solubility parameters (d), calculated according to the Hoftyzer and Van Krevelen method (Van Krevelen 1990), were lidocaine hydrochloride monohydrate(d = 19.3), amitriptyline hydrochloride (d = 20.4), sumatriptan succinate(d = 22.1), diclofenac sodium (d = 23.8), nicotinic acid (d = 25.7) and thiamine hydrochloride (d = 30.8). Three levels of drug loading were used, namely 5, 10 and20% w/w. Placebo patches containing no drug were also prepared for testing. After coating on to a polyester foil, all test preparations were dried at 40 C for 2 hours. A Bohlin Gemini 200 Advanced Rheometer (Malvern Instruments, UK) was used for all rheological testing. An amplitude sweep was first carried out to determine the linear viscoelastic region of each material under test. Rheological behaviour (interms of elastic modulus, G0 and loss modulus, G00) was then characterized via frequency sweeps at 32 C (w decreasing from 100 to 0.1 rad/seconds). The adhesive performance of each patch was then evaluated. The rheological criteria for acceptable PSA tack and peel properties have previously been established (Chu1991). Specifically, for good tack and peel performance, Chu identified G0100/G00.1(G0(at w = 100 rad/seconds)/G0(at w = 0.1 rad/seconds)) ratios of approximately5–300, together with G00.1 values (G0 at w = 0.1 rad/seconds) of approximately2 ¥ 104–4 ¥ 10 4 Pa. One-way analysis of variance tests with Scheffe post-hocanalys is were performed (using SPSS version 15) for elastic (G0 ) and loss modulus(G00 ) at 0.1 and 100 rad/seconds with a significance level = 0.05 and sample number n = 3.Results The drugs within each transdermal patch were found to be present in suspension form, implying that no drug was completely soluble in the adhesive.G0100/G00.1 ratios ranged from 10.9 to 26.6 (placebo = 11.7). G00.1 values ranged from 1.6 ¥ 104 to 3.7 ¥ 104 Pa (placebo = 1.84 ¥ 10 4 Pa). No patch showed a significant deviation from the Chu criteria. For drug-loaded adhesives, G00.1 values tended to increase with increasing drug concentration. Conclusions The acrylic polymer employed proved to be a versatile PSA in accommodating drugs with differing solubility parameters and concentrations when compared with the placebo. All patches exhibited adequate pressure-sensitive adhesive properties in terms of the Chu criteria. Hence, changes in drug solubility parameter and concentration did not significantly affect their adhesive performance. These findings will be of interest to the pharmaceutical industry specializing in transdermal patches and, in particular, to the manufacturers ofdrug-in-adhesive transdermal patches.