Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Solubility of Metoprolol Succinate
2.3. Preparation of Coated Pellets
2.3.1. Drug-Layered Starter Cores
2.3.2. Film-Coated Controlled Release Pellets
2.4. Characterization of Coated Pellets
2.4.1. In Vitro Drug Release Measurement
2.4.2. Pellet Swelling Monitoring
2.4.3. Osmotic Pressure Determination
2.5. HPC Leaching and Viscosity in Different Media
2.6. Preparation of Free Films
2.7. Water Uptake and Microstructure of Free Films
2.8. Mathematical Modeling
3. Results and Discussion
3.1. Drug Release from EC/HPC Film-Coated Pellets
3.1.1. Effects of the Media pH
3.1.2. Effects of Media Composition
3.2. Microstructure of Free EC/HPC Film
3.3. Influence of Media on HPC Properties
3.3.1. HPC Leaching from Coated Pellet
3.3.2. Viscosity of HPC Solution
3.4. Influence of Media on EC-Coating Film Properties
3.4.1. Drug Release From Pellets
3.4.2. Water Uptake and Swelling Study
3.4.3. Microstructure
3.5. Release Mechanism
3.5.1. Deionized Water and Phosphate Buffer at pH 6.8
3.5.2. HCl Solution at pH 1.2
3.5.3. Acetate Buffer at pH 4.5
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Solute | Solubility (mg/mL) | Osmolarity (π) of the Solution (mOsmol/kg) |
---|---|---|
Deionized water | 276.05 ± 3.27 | 0 |
HCl solution, pH 1.2 | 303.53 ± 2.84 | 174 ± 1.64 |
Phosphate buffer pH 6.8 | 249.20 ± 8.69 | 105 ± 1.81 |
Acetate buffer pH 4.5 (0.05 M) | 268.82 ± 9.21 | 70 ± 2.13 |
Acetate buffer pH 4.5 (0.005 M) | 259.93 ± 2.24 | 7 ± 1.12 |
Acetate buffer pH 4.5 (0.5 M) | 304.79 ± 9.62 | 730 ± 0.95 |
MS (Saturated solution-water) | - | 1050 ± 2.34 |
MS (Saturated solution-HCl) | - | 1294 ± 1.85 |
MS (Saturated solution-phosphate buffer) | - | 1160 ± 2.01 |
MS (Saturated solution-acetate buffer) | - | 1152 ± 2.16 |
Medium | RT (pure EC)-%-h | RT (80% EC)-%-h | RT (pure EC)/RT (80% EC) |
---|---|---|---|
Deionized water | 0.758 | 2.318 | 0.32 |
0.005 M, acetate buffer pH 4.5 | 1.025 | 2.987 | 0.34 |
0.05 M, acetate buffer pH 4.5 | 2.276 | 3.632 | 0.63 |
0.5 M, acetate buffer pH 4.5 | 4.680 | 6.189 | 0.76 |
Deionized Water | RT-%/h | %/h-(mOsmol/kg) | RD-%/h | Ro (RT-RD) | Ro/RT |
---|---|---|---|---|---|
20% | 2.318 | 0.002 | −0.056 * | 2.318 | 1.00 |
22% | 5.966 | 0.005 | 0.491 | 5.475 | 0.92 |
24% | 7.064 | 0.006 | 1.481 | 5.583 | 0.79 |
Phosphate buffer pH 6.8 | |||||
20% | 1.762 | 0.002 | −0.055 * | 1.762 | 1.00 |
22% | 5.033 | 0.005 | 0.241 | 4.792 | 0.95 |
24% | 6.418 | 0.006 | 1.226 | 5.192 | 0.81 |
HCl solution pH 1.2 | |||||
20% | 1.465 | 0.002 | −0.011 * | 1.465 | 1.00 |
22% | 7.694 | 0.004 | 3.050 | 4.644 | 0.60 |
24% | 12.53 | 0.005 | 7.135 | 5.395 | 0.43 |
Acetate buffer pH 4.5 | |||||
20% | 3.632 | 0.003 | 1.018 | 2.614 | 0.72 |
22% | 7.864 | 0.004 | 3.201 | 4.663 | 0.59 |
24% | 11.11 | 0.006 | 4.954 | 6.156 | 0.55 |
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Chen, L.; Yang, G.; Chu, X.; Gao, C.; Wang, Y.; Gong, W.; Li, Z.; Yang, Y.; Yang, M.; Gao, C. Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating. Pharmaceutics 2019, 11, 80. https://doi.org/10.3390/pharmaceutics11020080
Chen L, Yang G, Chu X, Gao C, Wang Y, Gong W, Li Z, Yang Y, Yang M, Gao C. Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating. Pharmaceutics. 2019; 11(2):80. https://doi.org/10.3390/pharmaceutics11020080
Chicago/Turabian StyleChen, Lu, Guobao Yang, Xiaoyang Chu, Chunhong Gao, Yuli Wang, Wei Gong, Zhiping Li, Yang Yang, Meiyan Yang, and Chunsheng Gao. 2019. "Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating" Pharmaceutics 11, no. 2: 80. https://doi.org/10.3390/pharmaceutics11020080
APA StyleChen, L., Yang, G., Chu, X., Gao, C., Wang, Y., Gong, W., Li, Z., Yang, Y., Yang, M., & Gao, C. (2019). Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating. Pharmaceutics, 11(2), 80. https://doi.org/10.3390/pharmaceutics11020080