Development of a pH-modulating vaginal film through direct powder extrusion 3D printing for on-demand, hormone-free contraception: a quality by design approach.

This study reports the development and optimization of a pH-modulating vaginal film fabricated via solvent-free direct powder extrusion 3D printing for localized sperm immobilization. The formulation incorporates lactic acid (90 mg), citric acid (50 mg), and potassium bitartrate (20 mg), the same clinically validated actives present in the Food and Drug Administration (FDA) - approved contraceptive gel Phexxi®. These actives were reformulated within a flexible polyethylene oxide matrix to enable a convenient, applicator-free solid dosage form. A Quality by Design (QbD) framework employing a four-factor, three-level Box-Behnken design was implemented to optimize independent variables like plasticizer concentration, printing temperature, extrusion pressure, and printing speed against dependent variables like disintegration time, film elasticity, and printability. The optimized film disintegrated within 84 s in simulated vaginal fluid and maintained vaginal pH within 3.5-4.0 over two hours under a six-fold excess of seminal fluid simulant, consistent with the acidic threshold required for sperm immobilization. FTIR and 1H NMR confirmed chemical stability post-processing, and three months of accelerated stability testing verified preservation of mechanical and functional performance. These findings establish a QbD-guided, on-demand vaginal film as a promising hormone-free contraceptive platform that combines a clinically validated pH-modulating composition with a convenient applicator-free solid dosage form.