The kinetics of sorption of solutes by plastic intravenous delivery systems
Creators: name: Kowaluk, Elzbieta Amelia
Publisher: name: University Of Tasmania
Year: 2023

description: The kinetics of the sorption of a number of solutes by the plastics of intravenous delivery systems were investigated. Models based on diffusion theory and compartmental analysis were developed and examined for .their ability to describe the uptake of a number of solutes from aqueous solutions stored in contact with the plastics. In deriving diffusion equations it has been assumed, firstly, that diffusion of solute in the plastic matrix is the rate-limiting step in the sorption process (matrix-controlled sorption) and, secondly, that both the plastic matrix and an interfacial resistance barrier contribute to the diffusional resistance encountered by the solute molecule (intermediate diffusion kinetics). The situation in which diffusion across the interfacial resistance barrier is the rate-limiting step was also considered. The ability of the diffusion and compartment models to describe and predict the sorption of the nonelectrolytes, nitroglycerin and diazepam, was examined. The diffusion model seemed to be the more satisfactory model in respect of both description and prediction of the drug uptake. The compartment model appeared to describe the drug uptake at earlier times, but was not able to describe the loss as equilibrium was approached; nor could that model be employed as a predictive method. The complete time-course, including equilibrium, of the sorption of nitroglycerin and diazepam was well-described by the (matrix-control) diffusion model. The diffusion model was also found to predict accurately the rate and extent of nitroglycerin and diazepam loss from solutions stored in plastic infusion bags of different sizes and containing various volumes of solution. The sorption of several weak electrolytes, specifically pnitrophenol, p-toluidine, warfarin sodium and trifluoperazine dihydrochloride, during storage of solutions of various pH in plastic infusion bags was also studied. The rate and extent of sorption varied with pH in a manner suggesting preferential uptake of the unionised species. It was assumed that only the unionised species was sorbed by the plastic matrix and the diffusion model was modified accordingly. The uptake of p-nitrophenol and p-toluidine was adequately described by the matrix-control diffusion model, confirming quantitatively the relationship between solute uptake and fraction unionised. However, the uptake of warfarin sodium and trifluoperazine dihydrochloride was significantly better described by the intermediate diffusion model. It appeared that the rate of uptake of the unionised form of these solutes was diminished due to the influence of interfacial or aqueous diffusional barriers. Solute lipophilicity, degree of ionisation and diffusion coefficient appeared to be important factors determining the relative contribution of the interfacial barrier and the plastic matrix to the overall diffusional resistance. Several approximations of the diffusion equations were considered. These approximations suggested that the rate and extent of solute uptake by the plastics of delivery systems at early times can be described by a single parameter. In general these approximations yielded parameter estimates consistent with those obtained by nonlinear regression using the full equations. A method of discriminating between matrix-controlled and intermediate sorption kinetics, based on these approximations, is also presented. The kinetics of solute loss from solution to plastic tubings during the course of an infusion was also investigated. The kinetics of loss could be interpreted in terms of diffusion-controlled sorption of the unionised solute by the plastic. Equations are presented to describe the availability of diazepam, and possibly other solutes, during infusion. The interaction of chlormethiazole edisylate with the plastic infusion systems displayed some unique characteristics, and these were further examined. It was found that, in some circumstances, chlormethiazole edisylate was not only sorbed by the plastic, but also permeated to the external environment. Furthermore, plasticisation of the polyvinyl chloride by chlormethiazole edisylate was observed. Some initial attempts at correlating the physicochemical characteristics of a range of solutes with their plastic sorption behaviour are also presented.