A novel orodispersible film load with dual-coated sustained-release microparticles for pediatric drug delivery

Abstract

Orodispersible films (ODFs), easy to administer, flexible in dosage, and free of choking and aspiration risks, have drawn widespread attention as pediatric formulations. However, it is a great challenge to endow ODFs with sustained release due to their fast disintegration. Herein, we designed a novel orodispersible film load with dual-coated sustained-release microparticles (SRMPs) for children using topiramate as a model drug. SRMPs with a particle size of 98.32 ± 0.22 µm, fabricated with a pellet core, a drug layer, and a coating layer, were prepared by two microparticle coating steps. The sustained-release orodispersible films (SRODFs) with uniform distribution of SRMPs and favorable disintegration time showed good formability, mechanical properties, and palatability. The factors affecting drug release of the SRMPs and the SRODFs were further explored. More importantly, pharmacokinetics study in human demonstrated that, although the SRODFs had a longer mean retention time, they were bioequivalence compared with the commercially available extended-release products (Qudexy® XR). A strong in vivo-in vitro correlation of the SRODFs was established. Notably, the SRODFs can be loaded with other drugs other than topiramate, offering a promising formulation option for pediatric patients with different diseases.