Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Determination of CBZ Equillibrium Solubility in F127 and SBE-β-CD Solutions
2.3. HPLC Analysis
2.4. Determination of CMC of F127 and CAC of SBE-β-CD in Buffer Solution pH 6.8
2.5. Estimation of the CBZ/F127 Association Constant, and the Stability Constant of CBZ/SBE-β-CD Complex
2.6. Free CBZ Fraction Estimation
2.7. Solubilizing Capacity Calculation
2.8. Light Scattering Measurements
2.9. Aggregation Number Determination
2.10. CBZ Partition Coefficients Determinations
2.11. Viscosity Measurements
2.12. Measurements of the CBZ In Vitro Permeability
3. Results and Discussion
3.1. CMC and CAC Measurements
3.2. Solubility Determinations
3.3. Solubilizing Capacity and Aggregation Behavior of F127 in the Presence of CBZ
3.4. Determination of the CBZ Partition Coefficients F127 Micelles/Buffer and SBE-β-CD/Buffer
3.5. Determination of the Membrane Permeability Coefficients
3.6. Pratio Evaluation
R = 0.9999; F = 6336.62; n = 3
3.7. Disclosing the Permeability Variations Using a Quasi-Equilibrium Transport Model
3.8. Correction of Permeability Coefficients for the Free Drug Concentration
4. Conclusions
5. Future Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CMC | Critical micelle concentration |
CAC | Critical aggregation concentration |
Ka | Association constant |
Kc | Stability constant |
Ctotal | Total CBZ concentration |
Cfree | Free drug concentration |
Cmicellar | Micellar (F127) drug concentration |
Ccomplex | Drug concentration in the CBZ/SBE-β-CD complex. |
CF127 | Concentration of F127 |
CSBE-β-CD | Concentration of SBE-β-CD |
ffree | fraction of free CBZ molecules |
Equilibrium CBZ solubility in the saturated solution of pure buffer | |
CBZ equilibrium solubility in the presence of F127 or SBE-β-CD | |
χ | Solubilizing capacity |
Nagg | Aggregation number |
Mw (micelle) | Molecular weight of F127 micelle |
Mw (monomer) | Molecular weight of F127 monomer |
Km/buf = KF127/buf | Micelle (F127)/buffer partition coefficient |
KSBE-β-CD/buf | SBE-β-CD/buffer partition coefficient |
RC | Regenerated cellulose membrane |
PDS | Polydimethylsiloxane-polycarbonate membrane |
J | Steady state flux through the membrane (µmol∙cm−2∙s−1) |
Papp | Permeability coefficient (cm∙s−1) |
Pratio | A ratio of Papp with the excipient to Papp with pure buffer solutions |
Permeability coefficient calculated within a quasi-equilibrium mathematical mass transport model | |
Absolute permeability coefficient for the free drug concentration | |
Difference between the permeability coefficients in pure buffer and the corrected values |
References
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Conditions | CMC (F127) (mol·L−1) | CAC (SBE-β-CD) (mol·L−1) |
---|---|---|
in the absence of CBZ | 1.640 (±0.066)∙10−4 | 1.716 (±0.069)∙10−2 |
CCBZ = 4.06∙10−4 mol·L−1 | 1.321 (±0.053)∙10−4 | 1.724 (±0.069)∙10−2 |
Cexipient (mmol·L−1) | Permeability Results | |||||
---|---|---|---|---|---|---|
Papp (cm∙s−1) | 1 | (cm·s−1) 2 | (mol·L−1) 3 | (cm·s−1) 4 | 5 | |
RC | ||||||
0 | (5.55 ± 0.15) × 10−5 | - | - | - | (5.55 ± 0.15) × 10−5 | - |
F127 | ||||||
1.33 | (3.22 ± 0.16) × 10−5 | 0.585 | 3.46 × 10−5 | 4.73 × 10−4 | 4.99 × 10−5 | 0.56 × 10−5 |
1.83 | (2.66 ± 0.08) × 10−5 | 0.484 | 2.52 × 10−5 | 3.77 × 10−4 | 5.86 × 10−5 | −0.31 × 10−5 |
2.30 | (2.03 ± 0.07) × 10−5 | 0.369 | 2.00 × 10−5 | 4.73 × 10−4 | 5.82 × 10−5 | −0.27 × 10−5 |
SBE-β-CD | ||||||
6.89 | (2.05 ± 0.08) × 10−5 | 0.373 | 1.81 × 10−5 | 4.46 × 10−4 | 7.15 × 10−5 | −1.6 × 10−5 |
13.78 | (1.34 ± 0.07) × 10−5 | 0.244 | 1.09 × 10−5 | 3.88 × 10−4 | 7.96 × 10−5 | −2.41 × 10−5 |
20.67 | (1.24 ± 0.06) × 10−5 | 0.225 | 7.74 × 10−6 | 5.59 × 10−4 | 1.05 × 10−4 | −4.95 × 10−5 |
PDS | ||||||
0 | (5.67 ± 0.17) × 10−7 | - | - | - | (5.67 ± 0.17) × 10−7 | |
F127 | ||||||
1.33 | (2.86 ± 0.16) × 10−7 | 0.504 | 3.54 × 10−7 | 4.64 × 10−4 | 4.41 × 10−7 | 1.26 × 10−7 |
1.83 | (2.53 ± 0.09) × 10−7 | 0.446 | 2.57 × 10−7 | 3.78 × 10−4 | 5.56 × 10−7 | 0.11 × 10−7 |
2.30 | (2.14 ±0.07) × 10−7 | 0.377 | 2.05 × 10−7 | 3.12 × 10−4 | 6.12 × 10−7 | −0.45 × 10−7 |
SBE-β-CD | ||||||
6.89 | (1.27 ± 0.08) × 10−7 | 0.224 | 1.85 × 10−7 | 4.40 × 10−4 | 4.66 × 10−7 | 1.01 × 10−7 |
13.78 | (7.96 ± 0.20) × 10−8 | 0.140 | 1.11 × 10−7 | 5.14 × 10−4 | 4.72 × 10−7 | 0.95 × 10−7 |
20.67 | (5.65 ± 0.15) × 10−8 | 0.100 | 7.91 × 10−8 | 5.00 × 10−4 | 4.76 × 10−7 | 0.91 × 10−7 |
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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
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(2):184. https://doi.org/10.3390/pharmaceutics16020184
Chicago/Turabian StyleVolkova, Tatyana, Olga Simonova, and German Perlovich. 2024. "Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine" Pharmaceutics 16, no. 2: 184. https://doi.org/10.3390/pharmaceutics16020184
APA StyleVolkova, T., Simonova, O., & Perlovich, G. (2024). Mechanistic Insight in Permeability through Different Membranes in the Presence of Pharmaceutical Excipients: A Case of Model Hydrophobic Carbamazepine. Pharmaceutics, 16(2), 184. https://doi.org/10.3390/pharmaceutics16020184