Pharmaceutical Development of Nitrosourea Compound for the Treatment of Neuroendocrine Tumours

Background: Nitrosoureas are chemotherapeutic alkylating agents, widely used in the treatment of malignant diseases. One of them (streptozotocin) is the standard for the therapy of neuroendocrine tumours. We synthesised a nitrosourea compound, aranoza, which has been effective in preclinical studies on experimental tumour models. Objectives: The current research deals with the development of the pharmaceutical dosage form of aranoza and the evaluation of the quality of the finished product. Methods: Sterilizing filtration followed by freeze drying was used to prepare the finished product. The acidity of the solutions was determined potentiometrically. Aranoza content in solution and lyophilisate was determined by spectrophotometry method. Results: We suggested the composition of the drug for parenteral use. The created product includes polyvinylpyrolidone and sorbic acid for solution stabilization and regulation of acidity, respectively. We also selected the method for aranozasolution preparation and showed that filters of mixed cellulose esters have optimal characteristics for filtration sterilisation. We chose lyophilisation to obtain a stable product: the freezing temperature was determined as -40°C to -45°C and the duration of freezing as 3–4 hr. The finished product has characteristics corresponding to requirements of the European Pharmacopoeia and State Pharmacopoeia of the Russian Federation and maintained its quality for the time of observation of 36 months. Conclusion: We created the algorithm for the development of a lyophilised antitumor drug, which allowed to obtain an appropriate pharmaceutical dosage form of a nitrosourea compound, aranoza, purposed for the treatment of neuroendocrine tumours.