Physicochemical stability of compounded midazolam capsules over a one-year storage period

Abstract

Abstract Objectives In patients suffering from chronic liver disease, the hepatic metabolism of drugs is perturbed and the metabolic capacity is difficult to assess. Midazolam could be used as a phenotypical probe to predict the metabolic capacity of CYP3A to adjust dosages of drug substrates of this cytochrome. In this context, a prospective clinical trial is going to be conducted in our institution and a hospital preparation of midazolam capsules suitable for the clinical trial was developed. The objective of the present work was to assess the physicochemical stability of the formulation over 12 months to set shelf life. Methods Three batches of 1 mg capsules were prepared using midazolam hydrochloride and microcrystalline cellulose as a diluent. The capsules were stored at ambient temperature and protected from light. To measure the evolution of the capsules content, a stability-indicating high-performance liquid chromatography (HPLC) method was developed with ultraviolet (UV) detection at 254 nm. Data were confirmed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method. Results After one year, midazolam hydrochloride content remained higher than 95% of the initial concentration in capsules. Conclusions The results show that 1 mg midazolam capsules are stable for 12 months at room temperature and under dark conditions.