Stability of temozolomide in solutions aimed for oral treatment prepared from a commercially available powder for infusion

Temozolomide (TMZ) is an alkylating agent with a broad spectrum of antitumor activity, including brain tumors in children. The oral use of TMZ is hampered by the lack of a suitable galenic formulation, since the capsules of TMZ (Temodal™) are large and difficult to swallow. A powder for preparation of a TMZ solution for intravenous administration (2.5 mg/mL) has recently been approved. A possibility to use this formulation for oral administration would facilitate TMZ administration.The aim of the present study was to investigate the stability of TMZ in solutions prepared from the commercially available powder for intravenous infusion.Solutions were prepared from the intravenous formulation by dissolving the powder in water. The degradation of TMZ was studied photometrically at 330 nm in two solutions, 2.5 mg/mL at room temperature (RT; 22°C) and 1.25 mg/mL at 5°C, prepared from the intravenous formulation.More than 90% of TMZ remained intact after storage for 9 days at RT (2.5 mg/mL) and 13 weeks at 5°C (1.25 mg/mL).The high stability of a TMZ solution prepared from the powder for infusion formulation makes it suitable for oral administration. Oral use of a TMZ solution facilitates administration of the drug to patients with difficulties to swallow capsules, and enables a more flexible and precise dosing.