Evaluation of a tube method for determining diffusion coefficients for sparingly soluble drugs

Evaluation of a non-steady state method using glass tubes for the determination of diffusion coefficients is the purpose of this study. Unlike capillaries, glass tubes accommodate a larger volume of solution, facilitating assay procedures. Tubes are more susceptible to convection than are capillaries, but this effect is anticipated and accounted for in experimental design and data treatment. Glass tubes, 66 or 90 mm in length and 2 mm outer diameter, were siliconized and then filled with aqueous drug solution and placed in a jacketed flask containing gently stirred solvent at 25 degrees C. Diffusion experiments were run from 140 to 168 hours. At the end of this time period, the tubes were removed from the flask, placed in an ultrasonic vibrator for one minute, and their contents assayed spectrophotometrically. Data collected using potassium chloride as the diffusant showed little tube-to-tube variability, demonstrating the precision of the tube method, while diffusion coefficients determined for benzoic acid and p-aminobenzoic acid using the tube method tested the accuracy of the method by comparing reasonably well with values obtained using standard methods such as the rotating disk, free boundary, and membrane cell. Experiments done with either hydrocortisone or sulfisoxazole as the diffusant demonstrated the appropriateness of the tube method for the study of the diffusion of sparingly soluble pharmaceutical solutes.