A new ultrasonic differential method for measuring diffusion coefficients of drugs inside small gel samples. application to the diffusion of lidocaine hydrochloride and lidocaine base inside a 25% pluronic ® F-127 gel

Abstract

A new method for the determination of the diffusion coefficient inside a solid matrix has been developed. The method is based on simultaneous, automatic, non-destructive measurements of the difference between the ultrasonic velocity (2 MHz) at two fixed positions within the solid matrix as a function of time. The differential technique eliminates problems arising from small temperature fluctuations and time stability of the electronics and increases the sensitivity with the result that the volume of the diffusion cell can be reduced to 1 ml. A data treatment procedure has been developed from which the diffusion coefficient can be obtained from the sound velocity data without any knowledge of the actual concentration, the partition coefficient, or possible interference of inter facial barriers. Thus the method avoids some of the substantial problems in measuring diffusion coefficients in many pharmaceutical systems. Application of the method to the diffusion of sodium chloride in a dilute gelatin gel gave a diffusion coefficient in agreement with the literature value. The diffusion coefficients of lidocaine hydrochloride and lidocaine base in a 25% (w/w) Pluronic ® F-127 gel were found to 2.5 × 10 −6 and 1.6 × 10 −6 cm 2 s −1, respectively, indicating a diffusion in the water channels between the polymer segments. Comparison with literature data obtained by the traditional release experiments showed the possible influence of the partition coefficient and the interfacial barrier on the diffusion process.