N06 - Dissolution Characteristics of Split and Crushed Levetiracetam Extended-Release Tablets in Comparison with Immediate-Release Formulation

Abstract: Background Levetiracetam (LEV) is a commonly used antiseizure medication in dogs, available as immediate-release (LEV-IR) and extended-release (LEV-XR) formulations. LEV-XR improves compliance by reducing dosing frequency but has limited utility in small dogs based on the minimum tablet concentration of 500 mg. Some clinicians advocate modifying LEV-XR tablets for administration during cluster seizures, but this practice has not been validated. Objectives To evaluate the effect of modifying LEV-XR tablets on in vitro dissolution rates and compare to that of intact LEV-IR. Methods Dissolution testing followed United States Pharmacopeia (USP) guidelines for LEV-XR. Intact, split and crushed LEV-XR 500 mg tablets and intact LEV-IR 500 mg tablets were each placed in a pH 6.0 buffer at room temperature and agitated at 100 rpm, with experiments run in triplicate. Samples were collected at 0, 0.5, 2, 4, 6, and 8 hours and analyzed using high-performance liquid chromatography. Results Percentage of drug release over time is depicted in figure 1. At 30 minutes, LEV-IR was completely dissolved; dissolution was 12.9 ± 0.6% for intact, 17.6 ± 0.7% for split, and 89.2 ± 4.6% for crushed LEV-XR. At 8 hours, intact, split, and crushed LEV-XR tablets reached 72.4 ± 2.4%, 88.8 ± 5.8%, and 95.5 ± 1.8% dissolution, respectively. Conclusions and Clinical Importance Splitting LEV-XR minimally affects extended-release properties, suggesting it may be a practical option for small dogs. Crushing LEV-XR mimics LEV-IR, indicating this modification may be useful for cluster seizures. Pharmacokinetic studies are needed to validate in vivo application.