In Vitro Plasma Compatibility Study of a Nanosuspension Formulation

Abstract

Lyophilized nanosuspension formulation intended for intravenous administration has been developed. The in-vitro plasma compatibility of the formulation was evaluated under conditions that mimic intravenous injection. After reconstitution of the lyophilized nanosuspension formulation with sterile water for injection, the drug was then further diluted with 0.9 % w/v NaCl or 5% w/v dextrose to make concentrations of 1.5 and 5.0 mg/mL with each diluent. The 1.5-mg/mL solutions were diluted with plasma in the ratio of 1:1 and 1:2, and the 5.0-mg/mL solutions were diluted with plasma in the ratio of 1:2 and 1:10, to simulate different intravenous infusion rates. Different contributing factors for particle aggregation upon mixing with plasma—such as the concentration of active ingredient, the types of diluents, the formulation/plasma ratio dependent upon infusion rate and the plasma flow rate, and the incubation time—were evaluated with respect to particle aggregation. It was found that aggregation occurred very rapidly in all conditions and that more aggregation takes place with higher drug concentrations in the mixture with plasma. It was also found that there was minimum aggregation at the concentration of 1.5 mg/mL when delivered at an infusion rate of 2.5 mL/min. This combination is recommended for further toxicological and clinical evaluation.