A strategy to estimate the intrinsic flux of a poorly water soluble substance for comparison with its release from lipid-core nanocapsules

Abstract

In studies on the release of drugs, antioxidants, vitamins, etc., from submicrometric particles, the released portion cannot be separated from that which remains entrapped in the carrier using conventional filtration methods due to the membrane cut-off. Thus, other methods, for example, ultrafiltration–centrifugation or dialysis with dialysis bags, which enable this separation are used. However, as the substances vehiculated in colloidal aqueous solutions are usually poorly water soluble substances, it is not easy to obtain their intrinsic flux (J0) value in aqueous solution. In this context, our objective was to develop a strategy to obtain the J0 value of a poorly water soluble substance dialysate from an aqueous solution aiming to compare it with its apparent flux (Japp) from an aqueous colloidal system allowing the evaluation of the effect of nanoencapsulation on the release rate of a lipophilic substance. Different hydroethanolic solutions of a poorly water soluble substance (benzophenone-3 (BZ3)) were dialyzed against hydroethanolic media using dynamic dialysis with bags. The Japp value of BZ3 in each system was plotted as a function of the proportion of organic solvent and the exponential mathematical equation of this relation was used to calculate the J0 value of the substance in aqueous solution. BZ3-loaded lipid-core nanocapsule suspensions (BZ3-LNC) were used as a model for colloidal nanocarriers. The Japp value obtained for the release from the BZ3-LNC suspension was around 14-fold lower than the J0 value, indicating that the encapsulation of BZ3 into the LNC system was able to slows its diffusion. The strategy developed allows the use of the J0 values of poorly water soluble substances in aqueous solutions to verify whether the nanoencapsulation can prolong, for example, the substance delivery on the biological environment.