Influence of a Double-Lumen Extension Tube on Drug Delivery: Examples of Isosorbide Dinitrate and Diazepam

Abstract

PurposePlastic materials such as polyurethane (PUR), polyethylene (PE), polypropylene (PP) and polyvinyl chloride (PVC) are widely used in double-lumen extension tubing. The purposes of our study were to 1) compare in vitro drug delivery through the double extension tubes available on the market 2) assess the plastic properties of PUR in infusion devices and their impact on drug delivery.MethodsThe study compared eight double-lumen extension tubes in PUR, co-extruded (PE/PVC) plastic and plasticised PVC from different manufacturers. Isosorbide dinitrate and diazepam were used as model compounds to evaluate their sorption on the internal surface of the infusion device. Control experiments were performed using norepinephrine known not to absorb to plastics. Drug concentrations delivered at the egress of extension tubes were determined over time by an analytical spectrophotometric UV-Vis method. The main characteristics of plastics were also determined.ResultsSignificant differences in the sorption phenomenon were observed among the eight double-lumen extension tubes and between pairs of extension tubes. Mean concentrations of isosorbide dinitrate delivered at the egress of double-lumen extension tubes after a 150-minute infusion (mean values ± standard deviation in percentage of the initial concentrations in the prepared syringes) ranged between 80.53 ± 1.66 (one of the PUR tubes) and 92.84 ± 2.73 (PE/PVC tube). The same parameters measured during diazepam infusion ranged between 48.58 ± 2.88 (one of the PUR tubes) and 85.06 ± 3.94 (PE/PVC tube). The double-lumen extension tubes in PUR were either thermosetting (resin) or thermoplastic according to reference.ConclusionsClinicians must be aware of potential drug interactions with extension tube materials and so must consider their nature as well as the sterilisation method used before selecting an infusion device.

Understanding and Characterizing the Drug Sorption to PVC and PE Materials

“…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.…”

Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump

“…Sorption generally occurs in the early phase of infusion, and the pattern is followed by a convection-interfacial resistance-diffusion model 7 . Diazepam sorption results are comparable to the double-lumen extension tube model 17 when the initial drug concentration is considered before delivery. Therefore, sampling time points can be modified so that sorption evaluation takes less time.…”

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

“…In a recent study, Foinard et al . 2 highlighted that thermoplastic PU were more prone to absorption of diazepam and isosorbide dinitrate than thermosetting PU. The polyurethane used in this study was of thermoplastic nature, and also showed a high tendency to promote diazepam sorption, which is coherent with their results.…”

“…It can affect drug solutions by releasing compounds into the infusate or by retaining the drug (sorption) thus potentially affecting infusion safety and effectiveness. Sorption phenomena can cause a loss of active pharmaceutical ingredient (API) 1,2 or protective excipients 3 and are mediated by different physicochemical parameters/properties 4–6 that are still incorrectly evaluated. The phenomena can be detailed in two steps: adsorption then absorption.…”

“…This issue was reported with PVC bags and tubings from the 80’s 4 with different drugs such as diazepam 8,9 , amiodarone 10 , isosorbide dinitrate 11 , insulin 12,13 . More recently, many studies also highlighted losses of drug during administration with PVC but also with non-PVC based catheters or IV tubings 2,14–17 . Even though the sorption issue has been known for a long time, the mechanisms involved during this phenomenon are not completely elucidated.…”