Formulation of sustained-release orodispersible film containing drug–resin complexes of donepezil hydrochloride

Purpose: This study was aimed at developing sustained-release orodispersible films (ODFs) based on drug–resin complexes (DRCs) to improve medication compliance with donepezil hydrochloride (DPH), the first-line treatment for Alzheimer’s disease. Methods: DPH was formulated as DRCs using a batch method to retard drug release and mask the bitterness of DPH. The effects of particle size, drug-to-resin ratio, and reaction temperature on the complexation efficiency, drug loading capacity, and particle size distribution were investigated. The resultant DRCs were evaluated for in vitro release, taste-masking efficiency, and physicochemical properties. The ODFs were prepared using DRCs of various particle sizes and their physical properties, in vitro release, and release kinetics were evaluated. Results: Both the complexation efficiency and drug loading capacity of DRCs increased with smaller particle sizes, higher temperatures, and drug-to-resin ratios close to 1. However, drug release depended only on particle size, which was inversely proportional to the release rate. Although the particle size of DRC was comparable to that of the corresponding resin, it slightly increased with increasing drug loading capacity. The bitterness of DPH was masked, and drug leakage was avoided owing to ionic bond formation. The ODFs showed good physical properties regardless of the particle size of the DRCs, and the release profile of the ODFs was equivalent to their corresponding DRCs. Conclusion: This study is the first to develop sustained-release ODFs of DPH. Their use could improve medication compliance in patients with Alzheimer’s disease.