Stabilization of Octastatin, a Somatostatin Analogue. Preparation of Freeze-Dried Products for Parenteral Injection

摘要

Octastatin (RC-160, vapreotide INN) is a somatostatin analogue being developed for use in oncological, entero-logic and neuroendocrine applications. The pharmaceutical form is a freeze-dried preparation for parenteral injection use. Three dosage forms containing 0.5, 1.5 and 15 mg of vapreotide base have been investigated. Various freeze-drying conditions, stabilizing agents, membranes for sterile filtration and heating procedures have been examined. The formulation with glutamic acid-sodium glutamate buifer as a stabilizing agent, the type of membrane for filtration and the freeze-drying procedure have been found appropriate for subsequent industrial production. No evident degradation was observed either after manufacturing, or after a three-week accelerated stability study at 50 °C and 70% relative humidity.