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

Abstract

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.

Surface modification of SiO2 nanoparticles for bacterial decontaminations of blood products

“…Materials that make up medical devices, such as blood storage bags and catheters have gradually evolved along with the development of plastic tubes [30,31]. Different materials or biomaterials such as thermoplastics (PVC and polyethylene), thermosetting polymers (cross-linked polyurethane, PUR), flexible elastomers (silicones and linear PUR), or cellulose can be used to fabricate catheters [32][33][34]. Polyethylenes and PVC can be functionalized with various materials, such as polyglycidyl methacrylate allowing biodegradation in physiological conditions [35].…”

Drug Interactions with Plasticized PVCs

“…Drug-polymer materials interactions represent therefore a major issue for the pharmaceutical industry in the delivery of insulin 19,20 and other drugs. 10,11,15,[21][22][23][24][25] A number of factors have been identified to impact on sorption: 26 the physicochemical properties of the drug itself (lipophilicity, pKa, isoelectric point, steric hindrance, concentration), the excipient composition, infusing process (flowrate, medical devices length), the physicochemical properties and chemical nature of the polymer material 27,28 such as polyethylene (PE), poylethylene terephthalate (PET), polyamide (PA) and the nature and amount of plasticizers. 10,15,22,23 A number of experimental procedures [9][10][11][21][22][23]26,29,30 have been developed to determine the drug concentration before/after passing through the medical devices by using High Performance Liquid Chromatography (HPLC) methods to quantify the difference in drug quantities.…”

“…A number of factors have been identified to impact on sorption: the physicochemical properties of the drug itself (lipophilicity, p K a , isoelectric point, steric hindrance, and concentration), the excipient composition, infusing process (flow rate and medical devices length), the physicochemical properties, and chemical nature of the polymer material , such as polyethylene (PE), poly­(ethylene terephthalate) (PET), or polyamide (PA), and the nature and amount of plasticizers. ,,, A number of experimental procedures − ,− ,,, have been developed to determine the drug concentration before/after passing through the medical devices by using high performance liquid chromatography (HPLC) methods to quantify the difference in drug quantities. Experimental procedures focusing on material analyses have also been investigated as an alternative approach, but they have not been yet able to completely describe the molecular mechanisms involved in drug sorption to MDs.…”

Insulin Adsorption onto PE and PVC Tubings

“…This loss of drug can induce a decrease of the active pharmaceutical ingredient (API) concentration [1][2][3] and thus lowers the treatment efficiency. 4 Another phenomenon can occur, namely the leaching defined by the migration of the additives into the drug solution affecting thus the product's safety through either the toxicity of leached substances or the degradation of some properties of the drug. [5][6][7][8] A loss of isosorbide dinitrate, tacrolimus, diazepam, amiodarone, insulin has been observed during infusions via PVC tubings.…”

“…These interactions can lead to drug sorption, which can take the form of an adsorption (surface interaction only) or an absorption (migration into the material). This loss of drug can induce a decrease of the active pharmaceutical ingredient (API) concentration − and thus lowers the treatment efficiency . Another phenomenon can occur, namely the leaching defined by the migration of the additives into the drug solution, affecting thus the product’s safety through either the toxicity of leached substances or the degradation of some properties of the drug. − …”