Study of the issues of maintaining stability of poloxamer-based systems during autoclaving

Introduction. Parenteral and ophthalmic in situ systems must be sterile. The selection of sterilization method is a key step in the development of sterile stimuli-sensitive systems, as an inappropriate method can lead to the degradation of the gel-forming polymer and the API, resulting in a loss of activity. Unfortunately, the stability of poloxamer-based thermosensitive systems during sterilization, as well as methods for their stabilization using protective agents, remains insufficiently studied.

Aim. The aim of the study was to investigate the stability of poloxamer-based systems during autoclaving and to develop methods for protecting them from the adverse effects of sterilization.

Materials and methods. Poloxamers used in the experiment included Kolliphor® P 407, Kolliphor® P 188, Kolliphor® P 338, and Kollisolv® P 124 (BASF, USA), as well as Emuxol-268 and Proxanol-168, provided by JSC "NIOPIK" (Russia). Disodium salt of ethylenediaminetetraacetic acid (EDTA) (LLC PCF "KhimAvangard", Russia) and xylitol ("Sladkiy Mir" LTD, Russia) were selected as protective agents. The samples were autoclaved at 121 °C for 20 minutes. Stability was evaluated based on the following parameters: appearance, pH, kinematic viscosity, and sol-gel transition temperature.

Results and discussion. Autoclaving of various combinations of poloxamers had a negligible effect on the stability parameters of the formulations. The addition of EDTA at high concentrations led to an increase in viscosity, as well as a decrease in pH and gel-forming ability of the formulations. After sterilization, gel precipitation was observed in all samples containing EDTA, but the original appearance of the formulations was restored within 5 days. The other parameters remained stable after autoclaving. The addition of xylitol had a negligible effect on the initial properties of the poloxamers, and the formulations retained stability after sterilization.

Conclusion. The results of the experiments showed that autoclaving is a suitable method for sterilization of systems based on various combinations of poloxamers. The addition of EDTA, especially at high concentrations, should be avoided due to its negative impact on the key parameters of in situ systems and the risk of gel precipitation during autoclaving. Xylitol does not affect the stability of poloxamers during sterilization. However, further research is needed to evaluate the potential of EDTA and xylitol as protective agents for the stabilization of other stimuli-sensitive systems.

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