Preparation of Nanosized Clusters of Irinotecan Hydrochloride Trihydrate for Injection Concentrate to Reduce Carbon Footprint

The surprisingly stable irinotecan hydrochloride trihydrate injection concentrate having a supersaturated concentration of 20 mg/mL at 25 °C was due to the frustration of 150-nm sized liquid-like nanosized clusters formed by the aggregation of dimers of 1.5 nm in an aqueous phase, evidenced by the non-linearity of van't Hoff plot and dynamic light scattering measurement. The adoption of this stable supersaturated solution at 20 mg/mL by manufacturers as the commercial concentration was beneficial due to the less volume being involved throughout the manufacturing, handling, storage and transportation of the commercial product, while also enabling a versatile on-site concentration adjustment by dilution prior to intravenous administration. Regarding the physical characteristic of the solid state of irinotecan hydrochloride trihydrate, it was found to exist as a channel hydrate as evidenced by single-crystal, and high-temperature X-ray diffraction experiments. Dehydration takes place at approximately 35 °C as demonstrated by thermogravimetric analysis. Because of its non-stoichiometric nature under various RH values revealed by dynamic vapor sorption, the irinotecan hydrate salt raw material must be kept at 25 °C or below, and under the relative humidity of 40% to 60% to maintain the original stoichiometric ratio of the raw material.