Gamma Irradiation of Ready-to-Use Injectable Aqueous Suspensions: Impact on Particle Size, Rheology, Interfacial...

Ready-to-use (RTU) long-acting injectable aqueous suspensions offer sustained drug release but present significant challenges for terminal sterilization. While aseptic processing is frequently used for suspension manufacturing, it lacks the sterility assurance of terminal sterilization. This work investigated the viability of gamma sterilization of model RTU aqueous suspensions containing varying polymer types and suspended drug loads. Comprehensive physicochemical characterization revealed that gamma irradiation did not affect the drug solid-state form in both model suspensions, and effectively stabilized particle size, notably stopping particle size growth observed in the non-irradiated GSK model suspension (control group). However, size exclusion chromatography (SEC) and HPLC analyses confirmed significant radiolytic degradation of polymeric surfactants and stabilizers (poloxamer 338 and PEG 3350) in both naproxen and GSK model suspensions, characterized by random chain scission and cross-linking of the polymer chains. This polymer degradation induced by radiolysis resulted in a measurable reduction in viscosity and injection force, thereby easing the force required to push suspension through the narrow needle bore of the syringe. Conversely, radiolysis-induced loss of suspension microstructure compromised long-term physical stability (resuspendability), leading to irreversible caking after 18 months of storage. These findings indicate that while gamma irradiation is a plausible terminal sterilization method for injectable suspensions, careful consideration must be given to formulation design to compensate for radiolytic polymer degradation and maintain suspension physical stability over the desired shelf life.