Development and stability study of glibenclamide oral liquid paediatric formulations for the treatment of permanent neonatal diabetes mellitus

Abstract

Background: Glibenclamide is a second-generation oral sulfonylurea used to treat neonatal permanent diabetes mellitus. It is more effective and safer than the first-generation agents. However, no liquid oral formulation is commercially available and, therefore, it cannot be used for individuals who cannot swallow the solid form. Objectives: To develop and study the physicochemical and microbiological stability of two liquid glibenclamide formulations for the treatment of permanent neonatal diabetes mellitus: two suspensions (2.5 mg/mL) - one using glibenclamide raw material and the other, glibenclamide tablets. Furthermore, high-performance liquid chromatography (HPLC) stability showed that the method is optimised and validated for analysis of glibenclamide in the formulations studied. Methods: Samples were stored at 4°C, 25°C and 40°C. The amount of glibenclamide in each formulation was analysed in duplicate using HPLC at 0, 7, 14, 28, 60 and 90 days. Other parameters were also determined - for example, the appearance, pH and morphology. Microbiological studies according to the guidelines of the US Pharmacopoeia for non-sterile products at 0 and 90 days were carried out. Results: All formulations remained physicochemically and microbiologically stable at three different temperatures during the 90-day study. Therefore, glibenclamide formulations can be stored for at least 90 days at ≤40°C. Conclusions: These formulations are ideally suited for paediatric patients who usually cannot swallow tablets. The proposed analytical method was suitable for studying the stability of different formulations.