Pharmaceuticals
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
By Valeria Frangione, Cristina Sensi, Milko Massimiliano Radicioni and 2 others.
Abstract
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.