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

摘要

Polyvinylchloride (PVC) has several uses and one of these is as theudprincipal constituent of containers used in the storage of pharmaceuticaludsolutions. It has been shown previously that the use of PVC containersudfor some liquid pharmaceutical systems has not been satisfactory in thatudthe solute may lose potency with time. Similarly, the use of PVC as audtubing is not always desirable.udIn this work, the effect of each of three physicochemical variables, soluteudconcentration, electrolyte concentration and temperature on the uptakeudof a number of model solutes by PVC infusion bags has beenudinvestigated. Additionally, a study on the kinetics of the sorption of theudmodel solutes by PVC tubing has been carried out and the influence ofudfactors such as solute concentration, flow rate, tubing diameter andudtubing length on the extent of solute uptake by PVC tubing has also beenudinvestigated.udIt has been shown that the extent of solute uptake by PVC infusion bagsudis independent of the inital concentration of the solute and that bothudtemperature and electrolyte concentration have significant effects on theudextent of solute loss. The Arrhenius equation is used to describe theudtemperature effect on solute uptake into PVC bags. The extent of soluteuduptake from solution in the presence of electrolytes without large ions isuda function of increasing ionic strength. A prediction model based on theuddiffusion model is used to describe the sorption profile of the modeludsolutes. 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 ofudcorrection factors for temperature and for vehicle ionic strength.udA well-stirred compartment model and a well-stirred diffusion modeludare examined for their ability to describe the uptake of the model solutesudfrom aqueous solutions infused through PVC tubings. It is shown that audbiexponential model which is a simplified form of both the well-stirredcompartmentudmodel and the well-stirred-diffusion model can be used toudadequately describe the sorption profiles of the model solutes during aud24-hour infusion period. Furthermore, it is found that, at a certain timeudafter the beginning of an infusion, the first exponential term of theudbiexponential model will approach zero and the biexponential formulaudwill be reduced resulting in the monoexponential form which is audgeneral form of the equation used to describe the uptake of all solutesudregardless of their affinity for PVC tubings.udThe solute uptake by PVC tubings has been found to be independent ofudthe initial concentration of the infusion solution while it is shown to beuda function of flow rate, tubing diameter, and tubing length. In order touddescribe the difference in the extent of sorption between two separateudkinetic runs conducted with differing flow rate, tubing diameter, and/ orudtubing length, a model based on chemical similarity theory wasuddeveloped. This allows for an approximation of the rate and extent ofudsolute uptake in one system from a knowledge of the uptake in audseparate system operating under different conditions. Results reportedudpreviously by other investigators for a number of drugs and thoseudpredicted using the proposed model are presented.udAn attempt was made to correlate the extent of sorption of the modeludsolutes by PVC infusion bags, or by PVC tubing, with selectedudphysicochemical properties of the solutes such as octanol-water partitionudcoefficient, dipole moment, intrinsic molecular volume andudsolvatochromic parameters.udThe plasticizers used in the formulations of PVC bags and tubings beingudstudied were identified. The infrared spectra and ultraviolet absorptionudspectra of the methanolic extracts of the PVC sheets cut from anudunprinted area of PVC bag and tubing reveal that the phthalate-typeudplasticizer, DEHP, was used in both formulations. Therefore, the DEHPwaterudpartition coefficients were determined for the model solutes andudthe utility of this value in predicting the uptake of the model solutes byudPVC materials was evaluated. Some attempts to relate chemicaludstructure and chemical interaction to solute sorption by PVC infusionudbags are described.