A Novel Lorazepam Orodispersible Film: Bioequivalence, Pharmacokinetic, and Tolerability Evaluation Compared with Film-Coated and Orodispersible Tablets in Two Randomized Crossover Studies in Healthy Subjects

Introduction: Lorazepam is a widely prescribed benzodiazepine available in multiple pharmaceutical formulations. A novel lorazepam orodispersible film (ODF) has been developed as an alternative dosage form designed to address administration challenges and enhance treatment adherence. Its pharmacokinetic profile, including the rate and extent of absorption, and its tolerability were evaluated in comparison with commercially available oral formulations in two bioequivalence studies. Methods: Two single-center, single-dose, open-label, randomized studies were conducted in healthy adults under fasting conditions. Study A was a three-way crossover pilot study comparing lorazepam 2.5 mg ODF (test, T) with film-coated tablets (Tavor®, reference 1, R1) and orodispersible tablets (Tavor® ORO, reference 2, R2). Study B was a two-way crossover pivotal study comparing T with R1. Treatments were separated by washout periods of ≥7 days. Pharmacokinetic parameters and point estimates (PEs), expressed as the ratios of least-squares geometric means (T/R1 and T/R2), were assessed. Results: In both studies, lorazepam pharmacokinetic profile was comparable across formulations, with similar Cmax and area under the curve (AUC) values. Peak concentrations were reached within 1–1.5 h for all treatments, and the elimination half-life was approximately 15–16 h. The 90% CIs for Cmax, AUC0–t, and AUC0–∞ for T versus R1 and R2 were within the 80–125% bioequivalence range. All treatments were well tolerated, with somnolence being the most frequent adverse event. Conclusions: Lorazepam 2.5 mg ODF demonstrated bioequivalence to both film-coated and orodispersible tablet formulations, with a comparable tolerability profile, supporting its potential as a convenient alternative formulation for lorazepam.