Prolonged release from orodispersible films by incorporation of diclofenac-loaded micropellets.

Prolonged drug release provided by multiple-unit dosage forms is highly beneficial to enhance the compliance and safety of the pharmacotherapy even for patients with swallowing deficiencies. To facilitate the intake for these patients, multiple-unit tablets and capsules have to be crushed or opened. An attempt to overcome these issues has been made by the introduction of orodispersible films (ODFs), which rapidly disintegrate within the oral cavity and facilitate the intake of oral solid dosage forms. The aim of this study was to develop a rapidly disintegrating ODF with prolonged release properties by incorporation of small-sized micropellets (MPs). MPs with a drug load of 70% were produced by wet extrusion and spheronization using Vivapur® MCG as pelletizing aid and diclofenac sodium (DS) as model drug. MPs were film-coated with an Eudragit® RS/RL coating and incorporated into the ODF-forming hypromellose solution. ODFs were produced by solvent casting technique. Disintegration times were determined using the PharmaTest® disintegration tester equipped with sample holders for ODFs. Dissolution studies were performed for MPs and ODFs. X-ray micro-computed tomography was used to visualize internal and external surface structures of MPs before and after release studies. MP-loaded ODFs show fast disintegration within 30 s, whereby film-coated MPs remain intact. Uncoated MPs are disintegrating thus revealing immediate DS release. In comparison, DS release was prolonged for film-coated MPs and corresponding ODFs. Incorporation of different amounts of MPs had no effect on the dissolution, but on mechanical properties of ODFs, which decrease with increasing amounts of MPs. The production of rapidly disintegrating ODFs with prolonged release properties for DS, representing a freely water-soluble drug, was feasible.