Correlation of the intravenous in-line drug delivery kinetics with the diluent flow rate, angle of internal flow, wettability, solubility and particle surface area

Abstract

The primary objectives of this work were to investigate various parameters that would potentially affect the delivery kinetics of drugs via an in-line intravenous (IV) delivery system and to establish a mathematical model to correlate the drug delivery kinetics with these parameters. The in-line delivery system contains a drug containing device which is placed between a parenteral solution (which is also termed as the diluent) container and a patient. The solid drug in the device is automatically dissolved by the diluent and administered to the patient as the diluent solution flows through the system via an administration set at a controlled flow rate. This system comprises numerous advantages over the conventional infusion systems, including labor-saving, convenient to use and minimizing human error. The delivery kinetics of this system was assessed using T Net95 which is defined as the time to deliver 95% of drug, excluding the lag time, via this system. The values of T Net95 for various drugs were experimentally determined in this study. A semi-empirical regression equation was used to fit the experimental data. In this equation, T Net95 is expressed in terms of the five parameters, the diluent flow rate (FR), angle of internal flow Θ, contact angle θ, solubility C s , and the particle surface area (SA). The regression analysis was performed using the statistical package (SAS) and the results indicated that the most important parameters affecting T Net95 are FR, Θ and θ for the drugs investigated. A close fit of the regression equation to the experimental data was observed, with R 2 equal to 0.99. The resulting equation is expressed as T Net95 = − 60.88 + 1980.7/FR + 330.88/Θ 1 2 + 15.34/ cos θ . Using this equation, the delivery kinetics of other drugs in this in-line system may be predicted, provided that the angle of internal flow Θ and the contact angle θ of the drugs are available or determined. In order to give a close prediction, the solubility of the drug of interest should be similar to the range of solubility investigated in this paper.