Fluorescence Quantification of Silicone Oil Release upon Contact with Liquid Therapeutic Formulations

TL;DR

This paper introduces a fluorescence-based method to measure silicone oil release in prefilled syringes when in contact with drug solutions.

Contribution

The novel contribution is a rapid, quantitative, low-volume screening protocol for evaluating silicone oil release in drug delivery systems.

Findings

A fluorescence-based protocol was developed to quantify silicone oil release from syringe plungers.

The method allows for rapid and low-volume evaluation of drug-container compatibility.

The protocol can help understand factors affecting silicone oil layer stability.

Abstract

Prefilled syringes are valuable drug delivery systems, offering convenience and precision dosing. Among the critical factors influencing their performance is the stability of the silicone oil layer, which acts as a lubricant, guaranteeing the gliding properties of the plunger. The silicone oil, if it comes in contact with therapeutic formulations, can be subject to drug–container interactions, potentially leading to silicone oil release into the solution, thereby altering the gliding properties of the syringe and leading to unwanted particle formation, compromising drug efficacy and safety. Different measurement techniques, such as visual inspection, dynamic light scattering and spectroscopic analysis, are used to assess silicone oil layer stability in prefilled syringes. However, a quantitative, rapid and low-volume screening method to rapidly evaluate container compatibility for therapeutic formulations is not available. Here, we present a multi-well-based screening protocol allowing users to quantify, through fluorescence, the silicone oil released into a solution upon contact with liquid formulations. Fluorescently labeled uniform silicone oil layers of the desired thickness are deposited in glass-bottom wells and exposed to typical formulations, containing surfactants and monoclonal antibodies. The release of silicon oil as a function of contact time is quantified using fluorescence calibration. Beyond its use as a screening tool to evaluate drug–container compatibility, our protocol can contribute to the fundamental understanding of the factors and mechanisms influencing silicone oil layer stability and, furthermore, to the optimization of drug delivery systems.

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