Microstructural and Mechanical Characterization of PVA-Based Drug Delivery Films Containing Menthol: Correlation Between SEM Morphology and Texture Analysis Across Three Manufacturing Methods

Introduction: Menthol, a naturally occurring terpene alcohol from Mentha piperita L., is incorporated into polyvinyl alcohol (PVA)-based pharmaceutical films for topical analgesia. Its high vapour pressure creates manufacturing challenges, inducing microstructural defects that compromise film mechanical performance. Characterizing the relationship between manufacturing-induced surface morphology and film mechanical properties is essential for rational biomaterial design in drug delivery applications.

Methods: PVA-based films (PVA 10%, glycerol 3%) containing menthol (5% w/w) and benzocaine (5% w/w) were manufactured by three methods: semi-solid extrusion 3D printing, solvent casting, and DOBOT MG400 robotic arm-assisted electrospinning (15 kV, 1 mL/h, 10 cm tip-to-collector distance). Blank excipient-only controls were prepared in parallel. Surface microstructure was characterized by scanning electron microscopy (SEM) at ×1,000 magnification. Mechanical properties were assessed by texture profile analysis: compression force, resilience, film burst strength (HDP/FSR probe), and rib seal strength (N/mm). The coefficient of variation (CV%) was calculated for all parameters.

Results: SEM revealed distinct method-dependent microstructural profiles correlating directly with mechanical performance. Solvent casting produced large irregular surface pores (up to 50 µm) from menthol volatility, corresponding to reduced burst strength (1202 ± 435 g, CV: 36.2%). 3D printing generated uniformly distributed controlled microporosity, yielding superior burst strength reproducibility (2369 ± 99 g, CV: 4.2%)—a 10-fold improvement over casting. Electrospun films preserved the intact nanofibrous architecture even with active compounds, demonstrating the highest compression resistance (37.5 ± 2.2 N, CV: 5.9%) and optimal rib seal strength (3.09 N/mm, CV: 7.7%). Menthol incorporation significantly reduced compression force in all methods compared to blank films, confirming matrix plasticization.

Conclusions: Manufacturing method critically determines microstructural and mechanical quality of menthol-containing PVA biomaterial films for drug delivery. 3D printing provides superior dimensional reproducibility; electrospinning preserves nanofibrous integrity; and solvent casting is most vulnerable to volatile compound-induced defect formation. SEM morphology directly predicts mechanical performance, supporting its use as a quality screening tool in pharmaceutical biomaterial development.