Prediction of the time course of the sorption of therapeutic drugs and other solutes by polyvinylchloride in static and dynamic pharmaceutical systems

Polyvinylchloride (PVC) has several uses and one of these is as the principal constituent of containers used in the storage of pharmaceutical solutions. It has been shown previously that the use of PVC containers for some liquid pharmaceutical systems has not been satisfactory in that the solute may lose potency with time. Similarly, the use of PVC as a tubing is not always desirable. In this work, the effect of each of three physicochemical variables, solute concentration, electrolyte concentration and temperature on the uptake of a number of model solutes by PVC infusion bags has been investigated. Additionally, a study on the kinetics of the sorption of the model solutes by PVC tubing has been carried out and the influence of factors such as solute concentration, flow rate, tubing diameter and tubing length on the extent of solute uptake by PVC tubing has also been investigated. It has been shown that the extent of solute uptake by PVC infusion bags is independent of the inital concentration of the solute and that both temperature and electrolyte concentration have significant effects on the extent of solute loss. The Arrhenius equation is used to describe the temperature effect on solute uptake into PVC bags. The extent of solute uptake from solution in the presence of electrolytes without large ions is a function of increasing ionic strength. A prediction model based on the diffusion model is used to describe the sorption profile of the model solutes. It is suggested that the sorption number which has been used to predict solute uptake by PVC bags needs to be adjusted by the use of correction factors for temperature and for vehicle ionic strength. A well-stirred compartment model and a well-stirred diffusion model are examined for their ability to describe the uptake of the model solutes from aqueous solutions infused through PVC tubings. It is shown that a biexponential model which is a simplified form of both the well-stirredcompartment model and the well-stirred-diffusion model can be used to adequately describe the sorption profiles of the model solutes during a 24-hour infusion period. Furthermore, it is found that, at a certain time after the beginning of an infusion, the first exponential term of the biexponential model will approach zero and the biexponential formula will be reduced resulting in the monoexponential form which is a general form of the equation used to describe the uptake of all solutes regardless of their affinity for PVC tubings. The solute uptake by PVC tubings has been found to be independent of the initial concentration of the infusion solution while it is shown to be a function of flow rate, tubing diameter, and tubing length. In order to describe the difference in the extent of sorption between two separate kinetic runs conducted with differing flow rate, tubing diameter, and/ or tubing length, a model based on chemical similarity theory was developed. This allows for an approximation of the rate and extent of solute uptake in one system from a knowledge of the uptake in a separate system operating under different conditions. Results reported previously by other investigators for a number of drugs and those predicted using the proposed model are presented. An attempt was made to correlate the extent of sorption of the model solutes by PVC infusion bags, or by PVC tubing, with selected physicochemical properties of the solutes such as octanol-water partition coefficient, dipole moment, intrinsic molecular volume and solvatochromic parameters. The plasticizers used in the formulations of PVC bags and tubings being studied were identified. The infrared spectra and ultraviolet absorption spectra of the methanolic extracts of the PVC sheets cut from an unprinted area of PVC bag and tubing reveal that the phthalate-type plasticizer, DEHP, was used in both formulations. Therefore, the DEHPwater partition coefficients were determined for the model solutes and the utility of this value in predicting the uptake of the model solutes by PVC materials was evaluated. Some attempts to relate chemical structure and chemical interaction to solute sorption by PVC infusion bags are described.