Background and Importance Infant tuberculosis treatment is a combined therapy, which entails two main issues: commercialised paediatric presentations scarcity and inadequate adherence. Isoniazid is indicated as a front-line treatment. In order to prevent isoniazid’s induced peripheral neuropathy, pyridoxine should be supplemented.

Aim and Objectives The aim of this study was to develop and study the physicochemical and microbiological stability of a combined isoniazid+pyridoxine oral liquid formulation.

Material and Methods Literature search was performed to study isoniazid + pyridoxine formulation stability. As there were no published data in this field, the active pharmaceutical ingredients physicochemical proprieties and quality conditions were checked in Pharmacopeia and scientific literature. Stability-indicating methods were conducted and validated according to the Methodological Guidelines for non-sterile products.

• Physical study: organoleptic characters (colour, odour, flavour); clarity and degree of opalescence; and pH. The pH-goal of combined doses to avoid any possible active ingredient degradation was settled at 5.

• Microbiological study: total aerobic microbial count <103 UFC/ml; total combined yeasts/moulds count <102 UFC/ml; and absence of Escherichia coli/ml.

• Chemical study: high-performance liquid chromatography (HPLC) analysis and method validation to quantify isoniazid+pyridoxine recommended acceptable purity limit (90–110%).

Results Isoniazid 50 mg/ml + pyridoxine 8,3 mg/ml oral liquid formulation was compounded using aqua conservans and 70% liquid sorbitol. Samples were stored at aliquots, light and non-light-exposed, at room and refrigerated temperature, for 28 days. Each sample was analysed at 0, 7, 14, 21 and 28 days.

Refrigerated samples stayed physically stable and pH measure was 4,8±0,15. Room temperature samples got darker, bitter and slightly acidified. The concentration of isoniazid and pyridoxine was found to be at day-28 50,6±0,6 + 8,2±0,2 at room temperature and 51,3±0,6 + 8,3±0,1 at refrigerated temperature, respectively. Moreover, all samples maintained microbiological stability.

The validated method proved to be selective and linear. It exhibited an adequate repeatability and intermediate precision with variation coefficient lower than 2%, and a recovery higher than 98%.

Conclusion and Relevance

• Isoniazid+pyridoxine oral liquid formulation was physicochemical and microbiologically stable stored at refrigerated conditions for 28 days.

• The proposed analytical method was viable to simultaneously determine two different active ingredients.

• It provides a reliable solution to enhance therapeutic adherence of children.

Conflict of Interest No conflict of interest.