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Protein drugs such as insulin are almost universally delivered via glass syringes lubricated with silicone oil. It is not uncommon for prefilled syringes (PFS) to become cloudy, which may affect bioavailability or total drug dose. To examine the role, if any, of the silicone oil lubricant in this process, a systematic evaluation of the degree of insulin denaturation and aggregation as a function of silicone oils of different molecular weights was undertaken. The former was measured using fluorescence changes of aqueous insulin/silicone dispersions, while the latter examined changes in turbidity as a function of mixing and silicone oil type; the results were confirmed at two different insulin concentrations and agitation speeds. Lower molecular weight silicones led to the most rapid denaturation and aggregation, and when examined in blends of silicones at a fixed viscosity of 1000 cSt, commonly used for syringe lubrication, more rapid denaturation/aggregation was noted in blends of silicones containing the largest fractions of low molecular weight materials. As a consequence, the molecular weight profile of silicone lubricants should be established prior to the preparation of prefilled syringes.

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Aggregation is frequently encountered during coating nanoparticles, especially when the core is not solid and the coating polyelectrolytes are weak. Here, the coating of a nanoliposome with two weak polyelectrolytes, alginate and chitosan, is investigated. First, quartz crystal microbalance with dissipation, atomic force microscopy, scanning electron microscopy, and energy dispersive spectroscopy analyses confirm the feasibility of firm adsorption of up to 16 layers of weak polyelectrolytes to the liposomal surface. Titrations are then performed to identify the lowest amounts of polyelectrolytes required to make eight saturated coating layers using the washless method. Significantly improved yields and reproducibility (almost 100%) are achieved, in addition to control over layer thickness. Attenuated total reflectance Fourier transform infrared spectroscopy studies confirm the success of layering. This is special since scientists always attempt to reduce nanoparticle aggregation by substituting the soft core, using one strong polyelectrolyte, or contending with lower yields or numbers of coating layers.