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

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 P_ratio 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.

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Materials

Carbamazepin (CBZ), C₁₅H₁₂N₂O, purity 98%, and pluronic F127 (M_w = 12,600 Da) were purchased from Acros Organics, Thermo Fisher Scientific, Geel, Belgium. Sulfobutylether-β-CD, purity 99%, was received from BLDpharm (https://www.bldpharm.com/ (accessed on 2 April 2019)). Potassium dihydrogen phosphate (purity ≥99%) and sodium hydroxide (purity ≥98%) were supplied by Merck.

The phosphate buffer pH 6.8 was made as follows: 27.22 g of KH₂PO₄ was dissolved in 1 L of water (Solution 1); 2 g of NaOH was added to 250 mL of H₂O (Solution 2). Then, 250 mL of Solution 1 and 112 mL of Solution 2 were mixed together and diluted with bi-distilled water to 1 L.

All the reagents and solvents were used as received. A FG2-Kit pH meter (Mettler Toledo, Switzerland) standardized with pH 4.00 and 7.00 solutions was used to check the pH of the prepared buffers.

Volkova, T.; Simonova, O.; Perlovich, G. Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine. Pharmaceutics 2024, 16, 184. https://doi.org/10.3390/pharmaceutics16020184

excipients formulation