In-situ investigation of drug diffusion in hydrogels by the refractive index method This work describes a simple but novel analytical method for in-situ monitoring of the diffusion process of drugs in hydrogels based on refractive index measurements(Figure 4). The diffusion process was monitored by recording the refraction of a laser beam passing through a triangular cell which allows the determination of changes in the refractive index distribution from the deviated distance of the linear beam. Compared to conventional methods this new method exhibits advantages such as more simplicity lower cost and rapidness. Further the refractive index method permits the determination of the concentration distribution of solutes in the hydrogels at any time during the diffusion process under nondestructive circumstances. The proposed method was successfully applied to the investigation of the diffusion process of cefazolin sodium a typical antibiotic in agarose gel. By employing the Fick second law the diffusion coefficients of cefazolin sodium in 0.5-3 wt % agarose gels were determined to be on the order of 10-6 cm2/s. A decrease in the experimental temperature resulted in a decrease in the diffusion coefficient of the drug in the gel. Through extrapolation according to the Kohlrausch law the diffusion coefficient of cefazolin sodium in water was also determined to be 3.67?0-6cm2/s very close to the value calculated from the Stokes-Einstein equation. The application of Amsden抯 model based on obstruction effects to the diffusion of cefazolin sodium in agarose gel revealed well fitting with a scaling constant for agarose gels in good agreement with the published data. It is demonstrated that this novel method can be used to study the molecular diffusion or transport in hydrogels and shows clear advantages including low cost simplicity and nondestructive measurements. Moreover although the novel method requires transparency of the gel system and no vigorous reaction existing between the diffusion solute and the gel it is still potentially useful for monitoring the blood drugs in the biomedical fields.

The result was published in Anal. Chem.2004 76 2087-2812 and Macromolecules 2005 online