Insulin Adsorption onto PE and PVC Tubings.

We investigate the adsorption of insulin onto PE and PVC materials by using HPLC measurements and computer simulations. We interpret the experiments by calculating the Gibbs free energy profiles during the adsorption process. The values of free energy of adsorption show a good agreement with the experimental measurements. The adsorption of insulin onto the different materials is characterized through the conformational changes with respect to its conformation in water and the interfacial regions, which are described by specific arrangements of polymer chains, water, insulin, and plasticizer molecules.

Critical Drug Loss Induced by Silicone and Polyurethane Implantable Catheters in a Simulated Infusion Setup with Three Model Drugs.

Silicone and polyurethane are biocompatible materials used for the manufacture of implantable catheters, but are known to induce drug loss by sorption, causing potentially important clinical consequences. Despite this, their impact on the drugs infused through them is rarely studied, or they are studied individually and not part of a complete infusion setup. The aim of this work was to experimentally investigate the drug loss that these devices can cause, on their own and within a complete infusion setup. Paracetamol, diazepam, and insulin were chosen as models to assess drug sorption. Four commonly used silicone and polyurethane catheters were studied independently and as part of two different setups composed of a syringe, an extension set, and silicone or polyurethane implantable catheter. Simulated infusion through the catheter alone or through the complete setup were tested, at flowrates of 1 mL/h and 10 mL/h. Drug concentrations were monitored by liquid chromatography, and the silicone and polyurethane materials were characterized by ATR-IR spectroscopy and Zeta surface potential measurements. The losses observed with the complete setups followed the same trend as the losses induced individually by the most sorptive device of the setup. With the complete setups, no loss of paracetamol was observed, but diazepam and insulin maximum losses were respectively of 96.4 ± 0.9% and 54.0 ± 5.6%, when using a polyurethane catheter. Overall, catheters were shown to be the cause of some extremely high drug losses that could not be countered by optimizing the extension set in the setup.

Understanding and Characterizing the Drug Sorption to PVC and PE Materials.

Characterizing the sorption of drugs onto polyvinylchloride (PVC) and polyethylene (PE) materials in terms of thermodynamic adsorption properties and atomistic details (local arrangements, orientation, and diffusion) is fundamental for the development of alternative materials that would limit drug sorption phenomena and plasticizer release. Here, a combination of experiments and sophisticated calculations of potential of mean forces are carried out to investigate the sorption of paracetamol and diazepam to PE and PVC surfaces. The simulated Gibbs free energies of adsorption are in line with the experimental interpretations. The polymer-drug-water interface is then characterized at the molecular scale by an in-depth investigation of local properties such as density, orientation, and diffusion.

Physicochemical Stability of Monoclonal Antibodies: A Review.

Monoclonal antibodies (mAbs) are subject to instability issues linked to their protein nature. In this work, we review the different mechanisms that can be linked to monoclonal antibodies instability, the parameters, and conditions affecting their stability (protein structure and concentration, temperature, interfaces, light exposure, excipients and contaminants, and agitation) and the different analytical methods used for appropriate physicochemical stability studies: physical stability assays (aggregation, fragmentation, and primary, secondary, and tertiary structure analysis), chemical stability assays and quantitative assays. Finally, data from different published stability studies of mAbs formulations, either in their reconstituted form, or in diluted ready to administer solutions, was compiled. Overall, the physicochemical stability of mAbs is linked to numerous factors such as formulation, environment, and manipulations, and must be thoroughly investigated using several complementary analytical techniques, each of which allowing specific characterization information to be harvested. Several stability studies have been published, some of them showing possibilities of extended stability. However, those data should be questioned due to potential lacks in study methodology.

Do bevacizumab solutions interact with silicone or polyurethane catheters during an infusion through implantable venous access ports?

This work aims to evaluate the possible impact of interactions between bevacizumab solutions and an implantable port equipped with a silicone or a polyurethane catheter after infusion through a complete infusion set-up in simulated use conditions. Physico-chemical and structural stability of bevacizumab solution was assessed by visual examination, subvisible particles counting, dynamic light scattering, size exclusion chromatography and ion exchange chromatography. Mechanical properties of the catheters were evaluated by measuring Shore A hardness, strain at break, strain at stress and Young's modulus. The physico-chemical surface state of the catheters was assessed by FTIR-ATR spectroscopy, scanning electron microscopy (SEM) and by water contact angle measurement. The analysis of the bevacizumab solution did not highlight any signs of instability or loss of active substance. Mechanical properties of both materials remained unchanged after the infusion. During material analysis, a decrease in water contact angle observed after infusion and was more pronounced for polyurethane catheters than for silicone, possibly due to bevacizumab adsorption or possible leachable extraction from the materials. Surface modifications were also noted at SEM. This study did not highlight any modifications that could alter the quality of the bevacizumab infusion, nor of the infusion catheter in polyurethane or silicone, despite a modification of surface hydrophilicity. Even if after a single infusion, implantable ports remained safe to use, they aim to be used for several infusion of various drugs during their lifetime, and further studies are needed to assess the impact of repeated infusions.

Stability of infliximab solutions in different temperature and dilution conditions.

Infliximab is a monoclonal antibody widely used for the treatment of inflammatory diseases. Over the past few years, many studies have assessed that monoclonal antibodies are prone to aggregation under stress conditions. The aim of this study was to investigate the stability of solutions of an infliximab biosimilar (Inflectra®) at different concentrations (0.4, 2 and 10 mg/mL). These solutions were separately submitted to three temperature conditions that are likely to happen during the drug dispensing system: -20 °C, 5 °C and 25 °C. To perform a complete characterization of infliximab physicochemical and structural stability, a wide range of analytical techniques was employed including: visual inspection, subvisible particles counting (HIAC), dynamic light scattering (DLS), size exclusion chromatography (SEC), cation exchange chromatography (CEX), and analysis of primary, secondary and tertiary structure. When stored at 25 °C, chemical instability was the main limiting factor (highlighted by CEX), while SEC showed only some acceptable variations. After a single freeze-thawing cycle, the amount of subvisible particles was significantly increased. Some variations were also visible in CEX and the hydrodynamic diameter was increased after thawing 10 mg/mL samples. In regard of these results, infliximab (Inflectra®) solutions should not be used after a single freeze-thawing cycle between reconstitution and administration to the patient. The results showed stability at 5 °C of up to 14 days for 10 mg/mL solutions and 90 days for 0.4 and 2 mg/mL solutions, whilst samples stored at 25 °C were stable only 7 days at 10 mg/mL and 30 days when diluted.