Determination of Diffusion Coefficients of Sodium p-aminosalicylate in Sheep Nasal Mucosae and Dialysis Membranes by Fourier Transform Infrared Horizontal Attenuated Total Reflectance Spectroscopy

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Abstract
Fourier transform infrared horizontal attentuated total reflectance (FT-IR-H-ATR) spectroscopy was employed to determine the diffusion coefficients of sodium p-aminosalicylate (PAS) in sheep nasal mucosae and dialysis membranes. The system configuration, which comprises a closed system with an aqueous layer and a membrane layer, represents diffusion from a solution of limited volume. Data analysis involved fitting a truncated (seven term) Fourier series to the total mass transport into the membrane as a function of time. Comparison of diffusion coefficients of PAS in dialysis membranes obtained by this technique to those obtained by a standard steady-state permeation method showed excellent agreement. Apparent diffusion coefficients were approximately 4.33 (+/- 0.38) x 10(-7) and approximately 9.62 (+/- 5.30) x 10(-7) cm2/s for dialysis membranes and sheep nasal mucosae, respectively. These values are substantially smaller than the diffusion coefficient of PAS in aqueous solution, indicating that the rate-limiting step was diffusion in the membrane. The effect of purified gastric mucin solution (concentration up to approximately 6% w/v) on the apparent diffusion coefficient of PAS in the membranes was also investigated. The results showed no statistically significant change in the apparent diffusion coefficient in the presence of mucin for either sheep nasal mucosae or dialysis membranes. Although it was reported that mucin in solution retards the diffusion of PAS as compared to buffer alone, the mass transport within the membrane was the rate-limiting step for this hydrophilic compound.