Physicochemical and microbiological stabilities of hydrocortisone in InOrpha suspending agent studied under various conditions.

Hydrocortisone is principally used as replacement therapy in adrenocortical deficiency states. In pediatric practice, posology ranges from 10 to 20 mg/m2 per day, divided in three doses, for the purpose of mimicking the nycthemeral cycle. Hydrocortisone is marketed in France in tablet form that contains 10 mg of the active ingredient. This galenic formulation is not suitable for pediatric use, and often requires a grinding operation or a dose fractionation to facilitate administration. To overcome this difficulty, the objective of this study was to develop and evaluate the physicochemical and microbiological stabilities of hydrocortisone in a sugar-free, alcohol-free, and paraben-free InOrpha suspending agent. The studied samples were formulated into a 2-mg/mL suspension and stored in glass bottles at two temperature conditions, between 2 degrees C to 8 degrees C and at room temperature). Two series of twelve samples were tested for physicochemical stability using high-performance liquid chromatography as well as for a microbiological status for 28 days (daily opening of the bottles from day 0 of compounding) and for 56 days (first opening at day 28 from compounding and daily opening for 28 consecutive days). The high-performance liquid chromatography method developed is linear, accurate, precise, and robust. On the other hand, a forced degradation study has demonstrated the selectivity and specificity of the method validated as stability indicating. In both storage conditions, high-performance liquid chromatography analysis showed that tested samples had concentrations ranging within 90% to 110% of the initial concentration for 28 consecutive days upon daily bottle opening and, for a maximum of 42 days with a first opening at day 28 from the compounding time. Microbiological status remained stable throughout the course of the study. Based on the data collected, the study led to the development of a new galenic formulation of hydrocortisone suitable for pediatric use which can be safely stored under refrigerated conditions or at room temperature for a maximum of 42 consecutive days.