In-situ dissolution and permeation studies of nanocrystal formulations with second-derivative UV spectroscopy

[Display omitted] One of the most difficult challenges in developing nanocrystal formulations is to determine the dissolution behavior of nanocrystal suspensions (nanosuspensions), which occurs within seconds. Mefenamic acid (MFA) is a poorly soluble drug thought to limit the dissolution rate for membrane permeation. In this study, in-situ dissolution-permeation studies of a nanosuspension of mefenamic acid (MFA) were carried out using second-derivative UV spectroscopy. This method enabled us to distinguish between the concentrations of dissolved MFA and nano-suspended MFA via in-situ measurement and showed an improved dissolution rate of the nanosuspension compared to that of the microsuspension. The dissolution-permeation study with second-derivative UV spectroscopy revealed that the improved dissolution rate due to nanosized MFA resulted in an increase in the permeated amount of MFA. In addition, the solubility of MFA determined by HPLC after filtration with a 0.02-μm filter indicated that enhanced solubility due to nanosizing also improves the permeability of MFA. Therefore, we concluded that the solubility and dissolution rate enhancements attained by nanosizing would be key factors in increasing membrane transportation of MFA. These novel in-situ dissolution-permeation studies using second-derivative UV spectroscopy offer considerable promise for developing and characterizing nanocrystal formulations.