Interpreting permeability as a function of free drug fraction: The case studies of cyclodextrins and liposomes

Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine

“…The values of approved the rule reported in [ 18 ] that is controlled by the free drug fraction. Following from the very low drug/CD binding constant ( Kc = 395.9 M −1 ), a rapid exchange of the CBZ/CD complex to free CBZ is possible.…”

“…The values of the experimental apparent permeability coefficients ( P app ) were recalculated, taking into account the free CBZ concentration in the donor solutions ( ) in order to obtain the absolute permeability coefficients values ( ) ( Table 2 ). The concentrations of the free CBZ in the donor solutions ( ) and the absolute permeability coefficients ( ) [ 18 ] were calculated using the values of f free using the following equations: …”

“…Interestingly, the authors estimated a direct proportion between the concentration of the molecularly dissolved drug and the respective fluxes, but no correlation of the apparent solubilities with fluxes was found. In the study of the permeability of three chemically diverse compounds, atenolol, ketoprofen, and hydrocortisone with cyclodextrins and liposomes, Tzanova et al [ 18 ] revealed that solubilizing with cyclodextrins may or may not vary drug permeation. In turn, in the case of liposomal systems, drug permeability can be directly correlated to the free drug concentration.…”

“…As it was reported [ 26 ], in an aqueous solution, CBZ rapidly transforms into CBZ dihydrate. The selection of CBZ was caused by its poor solubility that makes it a suitable substrate for cyclodextrins and surfactants, such as, for example, hydrocortisone and ketoprofen in the study of Tzanova et al [ 18 ]. Sulfobutylether-β-cyclodextrin and pluronic F127 were chosen as the excipients.…”

“…In this respect, in most cases, just the concentration of molecularly dissolved drugs seems to be taken into account when concerning the permeability of the drug in the context of solubility-enabling formulations [21]. However, as it was shown in the recent study by Tzanova et al [18], at high concentrations, the complex can also penetrate through the barrier. From all the premises, it seems reasonable to make additional investigations aimed at the elucidation of all the factors concerning the permeability of drugs in pharmaceutical formulations in order to make correlations regarding absorption rate.…”