Formulation and characterisation of metyrapone suppositories for the first effective long-term use in an infant with McCune-Albright syndrome-related Cushing syndrome.

OBJECTIVES: The aim of this project was to develop a rectal formulation of metyrapone suitable for application in an infant hospitalised with McCune-Albright syndrome (MAS)-related Cushing syndrome and to provide a detailed description of the formulation protocol including quality control parameters.

METHODS: Suppositories with a drug load of up to 100 mg metyrapone were prepared. Mass variation, content uniformity and drug release were analysed according to the guidelines set out by the European Pharmacopoeia. Monitoring of the drug content for 6 weeks allowed for estimation of the storage stability at 2-8°C.

RESULTS: A protocol for the reproducible preparation of suppositories with intended metyrapone content of 30-100 mg was established. The suppositories were well tolerated by the patient and the clinical outcome is promising. The suppository preparations complied with the regulations from the European Pharmacopoeia. Further, a stability of the rectal formulation of at least 1 month was confirmed, facilitating medication supply for home care.

CONCLUSIONS: An adequate and easy to follow protocol for preparation of high-quality metyrapone suppositories, with sufficient stability for practical use and fulfilling major pharmaceutical quality parameters, was established. The protocol can be easily replicated by skilled personnel in a community pharmacy facilitating treatment of the infant in home care.