Influence of Fabrication Techniques on the Physicochemical, Textural, Release and Skin Delivery Performance of Polyvinyl Alcohol-Based Transdermal Films Containing Menthol: A Comparative Study.

Background

Transdermal films are promising dosage forms for controlled delivery of active pharmaceutical ingredients through the skin. Polyvinyl alcohol (PVA)-based matrices are particularly attractive due to their biocompatibility, film-forming ability, and versatility. However, the development of films for volatile compounds such as menthol remains challenging due to high potential losses during processing and application. This study compares PVA-based transdermal films fabricated by 3D printing, solvent casting, and electrospinning, focusing on the effect of fabrication method on film properties, release behaviour, and skin delivery performance.

Methods

A comprehensive characterization included morphology, structure, thickness, moisture content, mechanical properties, adhesion, menthol content, in vitro release, ex vivo permeation, and stability.

Results

Fabrication method significantly influenced film microstructure, menthol entrapment, and stability. Menthol acted as a plasticiser, increasing thickness and moisture content while reducing mechanical strength via disruption of intermolecular interactions within the PVA matrix. The 3D-printed films exhibited the highest entrapment efficiency (14.40%, corresponding to 4.00% menthol content in the dried matrix) and superior menthol retention after 6 months (75.0%), compared to solvent-cast and electrospun films, due to their dense layered structure limiting volatile losses. All formulations showed biphasic release behaviour, strongly dependent on fabrication method. Electrospun films released menthol fastest (68.94% at 1 h), followed by solvent-cast films (63.48% at 1 h), whereas 3D-printed films exhibited a more sustained profile (46.14% at 2 h), reflecting differences in porosity and diffusion pathways. These structural differences also affected skin delivery, with 3D-printed systems demonstrating higher epidermal flux than the other formulations.

Conclusions

Overall, fabrication method governed film microstructure and thereby controlled menthol entrapment, release, and transdermal performance. Extrusion-based 3D printing offers a promising strategy for designing transdermal systems for volatile compounds with improved structural control and delivery efficiency.