Segmental-Dependent Solubility and Permeability as Key Factors Guiding Controlled Release Drug Product Development
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Solubility
2.3. Octanol-Buffer Distribution Coefficients
2.4. Biorelevant pH-Dilution Dissolution Studies
2.5. Parallel Artificial Membrane Permeability Assay Studies
2.6. Rat Single-Pass Intestinal Perfusion (SPIP)
2.7. Physicochemical Analysis
2.8. Ultra-Performance Liquid Chromatography
2.9. Statistical Analysis
3. Results
3.1. Solubility
3.2. Biorelevant pH-Dilution Dissolution Studies
3.3. Log D
3.4. Physicochemical Analysis
3.5. PAMPA Assay
3.6. Rat Intestinal Perfusion Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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pH | Solubility (mg/mL) | Corresponding D0 |
---|---|---|
1.0 | 0.021 (±0.004) | 4.720 |
4.0 | 2.320 (±1.090) | 0.043 |
7.5 | 0.035 (±0.002) | 2.880 |
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Markovic, M.; Zur, M.; Fine-Shamir, N.; Haimov, E.; González-Álvarez, I.; Dahan, A. Segmental-Dependent Solubility and Permeability as Key Factors Guiding Controlled Release Drug Product Development. Pharmaceutics 2020, 12, 295. https://doi.org/10.3390/pharmaceutics12030295
Markovic M, Zur M, Fine-Shamir N, Haimov E, González-Álvarez I, Dahan A. Segmental-Dependent Solubility and Permeability as Key Factors Guiding Controlled Release Drug Product Development. Pharmaceutics. 2020; 12(3):295. https://doi.org/10.3390/pharmaceutics12030295
Chicago/Turabian StyleMarkovic, Milica, Moran Zur, Noa Fine-Shamir, Ester Haimov, Isabel González-Álvarez, and Arik Dahan. 2020. "Segmental-Dependent Solubility and Permeability as Key Factors Guiding Controlled Release Drug Product Development" Pharmaceutics 12, no. 3: 295. https://doi.org/10.3390/pharmaceutics12030295
APA StyleMarkovic, M., Zur, M., Fine-Shamir, N., Haimov, E., González-Álvarez, I., & Dahan, A. (2020). Segmental-Dependent Solubility and Permeability as Key Factors Guiding Controlled Release Drug Product Development. Pharmaceutics, 12(3), 295. https://doi.org/10.3390/pharmaceutics12030295