Formulation study of a patch containing propranolol by design of experiments

Abstract

Objective: To evaluate the feasibility of a transdermal patch containing propranolol (PR).

Method: Skin penetration enhancers (SPEs) able to improve the skin permeability of PR were selected and a quality by design approach was applied to the development of the patch by a 2⁴ full factorial design. The permeation profile of PR from the formulations was assessed in in vitro permeation studies performed by using Franz diffusion cells and human epidermis as membrane. Finally, skin irritation was evaluated by the Draize test.

Results: N-methyl pyrrolidone (NMP) resulted as the best SPE: in addition, the critical factors influencing the PR diffusion through the human epidermis when loaded in the patch resulted in the matrix thickness (X₁, p = 0.0957) and PR content (X₃, p = 0.0004) which improved the flux; conversely, NMP lacked its enhancement effect when loaded in the patch and the increase in its concentration (X₄, p = 0.006) affected the drug permeation through human epidermis. The flux of optimal formulation was 12.7 μg/cm²/h. On the basis of the steady-state concentration and clearance of PR, the estimated patch surface was 100–120 cm², since the activity of PR is related to its Senantiomer and no in vivo bioconversion occurs.

Conclusion: A patch containing (S)-PR was prepared and the (S)-PR flux (13.3 μg/cm²/h) permitted to confirm the suitability of a transdermal administration of PR. In particular, the use of a 50 μm thick methacrylic matrix containing 8% (S)-PR and 15% NMP can allow to develop a patch non-irritating to the skin, in order to ensure a constant permeation flux of PR over 48 h.

• Enantiomer
• in vitro skin permeation
• propranolol
• quality by design
• skin irritation
• transdermal patches