Extemporaneous Isoniazid Mixture: Stability Implications

Abstract

Background: Isoniazid mixtures are compounded in Australia using commercially available isoniazid tablets. Aim: To determine the stability of isoniazid 10 mg/mL mixture compounded from commercially available isoniazid tablets. Method: The stability of the compounded isoniazid mixture stored at a range of temperatures (4–60 °C) was assessed with high performance liquid chromatography. Differential scanning calorimetry was used to investigate the compatibility of isoniazid with the excipient, lactose. Results: The compounded isoniazid mixture exhibited significant degradation (≥ 10% after 3 days at 4 and 25 ºC), whereas the control (using isoniazid powder) retained desired stability (> 90% at 30 days) under identical conditions. A replicate control formulation, spiked with lactose, produced statistically similar degradation profiles to that of the compounded isoniazid mixture (p > 0.05), indicating lactose to be responsible for the degradation of isoniazid. The thermoanalytical studies demonstrated an incompatibility between isoniazid and lactose (broadening and shifting of melting endotherm of isoniazid at 171.46 ºC). Conclusion: The British Pharmaceutical Codex specifies the use of isoniazid powder for compounding isoniazid mixture. This study highlights the importance for stability evaluations on all modified extemporaneous preparations in order to ensure that quality pharmaceuticals are delivered to patients.