Prolonged drug release properties for orodispersible films by combining hot-melt extrusion and solvent casting methods

Abstract

Orodispersible films (ODFs) are an advantageous dosage form to accomplish patient convenience and compliance in oral drug delivery. They provide a number of special application features, such as the ease of administration without water and suitability for patients with swallowing problems. However, this promising dosage form has been limited to immediate release formulations so far. The aim of this study was to develop a thin film produced by solvent casting, which is rapidly disintegrating when placed in the mouth, but which provides prolonged drug release characteristics by incorporating drug-loaded matrix particles (MPs). MPs were produced by hot-melt extrusion and subsequent milling, using theophylline anhydrous as model drug and Eudragit^® RS as matrix-forming agent enabling prolonged drug release. ODFs were manufactured using hypromellose as film former. Dissolution studies were performed to investigate the kinetics and the duration of drug release. Additionally, disintegration time was determined using the PharmaTest^® disintegration tester equipped with a specific sample holder for ODFs. All produced ODFs containing theophylline-loaded MPs show fast disintegration while the drug release was prolonged. The degree of release prolongation increases with increasing sizes of incorporated MPs. Matrix-controlled release kinetics were found for ODFs containing MPs with at least 315 µm in size. In summary, the production of fast disintegrating ODFs with prolonged release properties was feasible. Furthermore, freely adjustable dissolution profiles could be realized for ODFs by incorporating MPs of various particle sizes.

Keywords: Dissolution kinetics; Fast disintegrating films; Hot-melt extrusion; Matrix particles; Multiple unit dosage form; Orodispersible films; Prolonged drug release; Solvent casting.