Silicone adhesive, a better matrix for tolterodine patches—a research based on in vitro/in vivo studies

Abstract

Objective: To design and optimize a drug-in-adhesive (DIA) type transdermal patch for tolterodine (TOL) based on acrylic and silicone matrixes.

Methods: Initial in vitro studies were conducted to optimize the formulations. Two types of adhesive matrixes, drug loading, and enhancers were evaluated on the TOL transport across rabbit skin. For in vivo studies, patches were administered to rabbit abdominal skin. Pharmacokinetic assessments were performed based on plasma level of TOL up to 28 h for acrylic patch and 52 h for silicone patch after topical application.

Results: The final formulation of acrylic adhesive type patch consisted of 10% TOL (w/w) and 5.8 × 10⁻⁴ mol isopropyl myristate (IPM) and 2.9 × 10⁻⁴ mol Span 80 in per unit gram (mol/g) of adhesive, while 2.5% TOL (w/w) and 2.9 × 10⁻⁴ mol/g IPM for silicone adhesive type patch. Comparison of the pharmacokinetic parameters between two types of patches showed that the steady-state concentration of silicone type patch was 2-fold higher than that of acrylic type patch being 0.97 mg/L versus 0.49 mg/L, and the absolute bioavailability was 27.5% for silicone type patch and 6.3% for acrylic type patch, respectively. In addition, the prediction of in vivo drug level from the in vitro permeation data of silicone adhesive formulation was in good agreement with actual observed concentration data in rabbits.

Conclusion: These results indicate that the silicone type of TOL patch is an appropriate delivery system for the treatment of overactive bladder (OAB).

Keywords::

• Tolterodine
• transdermal patch
• silicone adhesive
• acrylic adhesive
• in vitro studies
• in vivo studies