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

Abstract

The present study reports the effects of two pharmaceutical excipients of differing natures—non-ionic surfactant pluronic F127 (F127) and anionic sulfobutylether-β-cyclodextrin (SBE-β-CD)—on the permeation of the model compound, carbamazepine (CBZ). The permeability coefficients of CBZ at three concentrations of the excipients were measured through two different artificial barriers: hydrophilic cellulose membrane (RC) and lipophilic polydimethylsiloxane–polycarbonate membrane (PDS). The equilibrium solubility of CBZ in F127 and SBE-β-CD solutions was determined. The micellization, complexation, and aggregation tendencies were investigated. Systemically increasing the solubility and the reduction of permeation upon the excipients’ concentration growth was revealed. The quantitative evaluation of the permeability tendencies was carried out using a Pratio parameter, a quasi-equilibrium mathematical mass transport model, and a correction of permeability coefficients for the free drug concentration (“true” permeability values). The results revealed the mutual influence of the excipient properties and the membrane nature on the permeability variations.

Controlling the Solubility, Release Rate and Permeation of Riluzole with Cyclodextrins

“…The importance of evaluating the solubility/permeability trade-off in vitro in the early stages of the drug delivery process is undeniable since it can help to avoid unwanted variations in permeability and allows to cut down the expenses on the costly in vivo experiments. As it was demonstrated for different cyclodextrins [ 29 , 30 , 31 ], being an advantageous tool in solubility enhancement, in many cases (but not always) cyclodextrins reduce membrane permeability, as a result of decreasing the free (uncomplexed) fraction of the drug molecules [ 32 ]. In this case, using the water-soluble biopolymers that interact with CDs, replacing the drug molecules from CDs and increasing the free fraction of drug available for permeation can be useful.…”