Dissolution Characteristics of Split and Crushed Levetiracetam Extended-Release Tablets in Comparison With Immediate-Release Formulation

Abstract

Levetiracetam (LEV) is a commonly used antiseizure medication in dogs, available in immediate-release (LEV-IR) and extended-release (LEV-XR) formulations. LEV-XR improves owner compliance with less frequent dosing, but its lowest concentration tablet (500 mg) often exceeds recommended doses for small dogs. This study evaluated how modifying LEV-XR tablets affects dissolution rates, comparing intact, split, and crushed LEV-XR tablets with intact LEV-IR tablets. Dissolution testing followed United States Pharmacopeia (USP) guidelines for LEV-XR tablets. Tablets were placed in a buffer solution (pH 6.0) and agitated at 100 rpm. Samples were collected at 0, 0.5, 2, 4, 6, and 8 h, then analyzed by high-pressure liquid chromatography (HPLC) using a USP reference standard. Results indicated that splitting LEV-XR tablets slightly increased drug release compared to intact tablets, while crushing eliminated extended-release properties, mimicking LEV-IR dissolution. These findings suggest that splitting LEV-XR tablets may be a viable strategy for dosing small dogs without compromising sustained release. Conversely, crushing LEV-XR tablets may be useful for rapid drug release in cluster seizure protocols. Future pharmacokinetic studies are needed to confirm if these in vitro results correlate with in vivo performance for both maintenance and emergency seizure management in dogs.

Keywords: antiseizure medication; canine epilepsy; cluster seizure protocol; in vitro dissolution; tablet modification.

FIGURE 1

Mean (±SD) percentage of drug release from 500 mg LEV‐XR tablets, including intact tablets, split tablets, and crushed tablets, as well as intact 500 mg LEV‐IR tablets (n = 3 for each). Dissolution testing was conducted in a phosphate buffer at pH 6.0, stirred at a rate of 100 rpm.