Development and characterization of an hydrocortisone based oral dispersible thin film for paediatric treatment

Congenital adrenal hyperplasia causes a deficiency in adrenal glucocorticoid/mineralocorticoid biosynthesis. In the pediatric population, glucocorticoid replacement is achieved with hydrocortisone. Orodispersible thin films (ODFs) delivered into the mouth cavity are a novel drug preparation enabling adaptable dosing and better patient adherence. The purpose of the study was to develop and characterize an optimal ODF formulation containing hydrocortisone using solvent casting method, that could be made in hospital pharmacy. A variety of preparation methods, gel casting formulations using hydrocortisone or hydrocortisone hemissuciante (HMS) were investigated and further optimized. A stability indicating assay for the simultaneous quantification of hydrocortisone and HMS has been developed. ODFs were characterized by visual and manual inspections and by testing for uniformity of mass, content, and thickness. Disintegration of the ODF formulation was investigated and compared with a commercially produced ondansetron containing ODF (Setofilm^®). When optimised, ODFs are thin, flexible and transparent, making them suitable for production in hospital pharmacy with standard production facilities. Unlike the water-insoluble hydrocortisone, HMS loaded casting gel successfully satisfied the tests, including content uniformity. Disintegration appeared acceptable as compared with Setofilm®. The ODF formulated with HMS enables accurate hydrocortisone content to be achieved, thus opening new possibilities for use in pediatric patients.