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

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.

Determination of diffusion coefficients of peptides and prediction of permeability through a porous membrane

“…Therefore, the diffusion of such drugs immediately after administration of the delivery systems should be examined in detail (Weiss 1999;Salvetti et al 2002). The diffusion coefficient (D) of peptide and protein drugs having a relatively high molecular weight is lower than that of common therapeutic agents, and this value can vary with changes in conformation Salamat-Miller et al 2002) and interaction with other molecules (Bhat et al 1996;Nardviriyakul et al 1997;Larhed et al 1998). In some reports, the diffusivity of peptide and protein drugs during the processes of release and membrane permeation has been examined to optimize the delivery systems (Aso et al 1998;Agarwal et al 2001;Choi & Kim 2003).…”

“…The most important process related to the diffusion of drugs during their administration to mucous membranes is absorption (Nardviriyakul et al 1997;Larhed et al 1998). Since the absorption rate of higher-molecular-weight hydrophilic drugs is low, absorption enhancement is needed for the delivery of sufficiently high amounts.…”