Impact of alternative materials to plasticized PVC infusion tubings on drug sorption and plasticizer release

Abstract

Medical tubings in plasticized polyvinylchloride (PVC) are widely used for the infusion of medications but are known in some cases to cause content-container interactions (drug sorption and plasticizer release). The aim of this study was to assess interactions between drugs and five alternative materials to a reference plasticized PVC intravenous (IV) infusion tubing: three were PVC coextruded with polyethylene (PE), polyurethane (PU) or a thermoplastic elastomer (Styrene-EthyleneButadiene-Styrene (SEBS)) and two were SEBS or thermoplastic olefin (TPO) monolayer tubings. Diazepam and insulin were chosen as respective reference of absorption and adsorption while paracetamol acted as a negative control. The concentration of each drug was quantified with liquid chromatography to evaluate a potential loss after a static contact condition and simulated infusion at 1 mL/h and 10 mL/h dynamic condition by an electric syringe pump. A characterization of each material’s surface was performed by Fourier transform infrared spectroscopy in attenuated total reflection mode (ATR-FTIR) and by measurement of surface zeta potential. Plasticizer release was quantified by gas chromatography coupled with mass spectrometry (GC-MS). For all tubings except PVC/PU, no loss of paracetamol was observed in any condition. Diazepam sorption appeared to be less important with PVC/PE, PVC/SEBS, SEBS and TPO tubings than with PVC, but was more important when using PVC/PU tubings. PVC tubings induced the least loss of insulin amongst all the studied materials. Surface analysis by ATR-FTIR highlighted the presence of a plasticizer (that could be attributed to Tris (2-Ethylhexyl) Trimellitate (TOTM)) in the coextruded SEBS layer of PVC/SEBS, which could have influenced drug sorption, probably as a consequence of a migration from the PVC layer. Coextruded PVC/SEBS and PVC/PE presented the lowest zeta potential of all studied materials with respective values of −39 mV and −36 mV and were related to the highest sorption of insulin while PVC/PU with the highest zeta potential (about −9 mV) presented the highest absorption of diazepam. Coextruded layered materials appeared to have a lower plasticizer release than PVC alone. As a conclusion, PVC/PE and thermoplastic elastomers alone or coextruded with PVC could be interesting alternatives to PVC tubings with regards to sorption phenomena and plasticizer release.

Understanding and Characterizing the Drug Sorption to PVC and PE Materials

“…The radial distribution functions between drugs and water molecules in bulk water, given in Figure S6 of the Supporting Information, show that these two molecules are rather considered as lipophilic in line with their octanol-water partition coefficients. 4 (log P = 3.1 and 0.9 for diazepam and paracetamol, respectively).…”

“…A loss of isosorbide dinitrate, tacrolimus, diazepam, amiodarone, insulin has been observed during infusions via PVC tubings. [2][3][4][5][6][7][8][9] These losses of API by sorption can require an adjustment of the dose administered, based on the expected biological effect of the drug. Sometimes, rinsing the tubing by the drug before its administration is a possible way to limit these interactions.…”

“…Sorption (including the adsorption of a drug to the polymer surface, absorption into the polymer matrix, and permeation) can affect the efficacy and result in the loss of an important component, such as an active pharmaceutical ingredient (API) − or an excipient . This can lead to ineffective or variable drug responses after the administration of injectable drugs, and makes it difficult to control the concentration of the delivered drug.…”

“…This can lead to ineffective or variable drug responses after the administration of injectable drugs, and makes it difficult to control the concentration of the delivered drug. A loss of isosorbide dinitrate, tacrolimus, diazepam, amiodarone, and insulin has been observed during infusions via PVC tubings. − These losses of API by sorption can require an adjustment of the dose administered, based on the expected biological effect of the drug. Sometimes, rinsing the tubing with the drug before its administration is a possible way to limit these interactions.…”

Do plasticized polyvinylchloride and polyurethane infusion sets promote infliximab adsorption?

“…As such, adsorption phenomena can be a major concern during the infusion process since the drug lost is not administered to the patient and means a loss of effectiveness of the treatment. Infusion sets are medical devices used to connect infusion bags with the catheter, and are generally about 150-200 cm long, and are also known to cause drug loss and potentially release toxic compounds [7,8]. The objective of this study was therefore to evaluate potential adsorption phenomena of infliximab during administration through Polyvinylchloride (PVC) and Polyurethane (PU) infusion sets.…”