Factors That Influence Sustained Release from Hot-Melt Extrudates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Hot-Melt Extrusion
2.2.2. Homogeneity of Flurbiprofen Content in the Extrudates
2.2.3. Differential Scanning Calorimetry (DSC)
2.2.4. X-ray Powder Diffraction Analysis (XRPD)
2.2.5. Milling of the Extrudates into Various Particle Size Ranges
2.2.6. Dissolution Testing
2.2.7. HPLC Analysis
2.2.8. Data Presentation and Statistics
3. Results
3.1. Hot-Melt Extrusion
3.2. Content Uniformity
3.3. DSC
3.4. X-ray Powder Diffraction Analysis
3.5. Dissolution Testing
3.5.1. Dissolution Testing of the Eudragit RL Extrudates: Drug Loading Effect
3.5.2. Dissolution Testing of the Eudragit RL Extrudates: Effect of Particle Size
3.5.3. Dissolution Testing of the Eudragit RL Extrudates: Effect of Stirring Rate
3.5.4. Dissolution Testing of the Eudragit RS Extrudates: Effect of Drug Load
3.5.5. Dissolution Testing of the Eudragit RS Extrudates: Effect of Particle Size
3.5.6. Dissolution Testing of the Eudragit RS Extrudates: Effect of Stirring Rate
3.5.7. Dissolution Testing of the Commercial Product, Cebutid LP
4. Discussion
4.1. DSC and XRPD
4.2. Loading Capacity
4.3. Dissolution Testing
4.3.1. Effect of Particle Size
4.3.2. Effect of API Load
4.3.3. Effect of Polymer Type
4.3.4. Effect of Stirring Speed on Release from Extrudates
4.3.5. Commercial Product vs. Extrudates
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Flurbiprofen | Eudragit RL | Eudragit RS | |
---|---|---|---|
Melting temperature | 110–111 °C a 114–118 °C b | - | - |
Glass transition temperature | −8.15 °C | 63 °C | 64 °C |
Degradation temperature | 184 °C | 166 °C | 170 °C |
Components | 20% Flurbiprofen | 25% Flurbiprofen | 33% Flurbiprofen | 25% Flurbiprofen | Function |
---|---|---|---|---|---|
Flurbiprofen | 20% | 25% | 33% | 25% | API |
Talcum | 2.5% | 2.5% | 2.5% | 4% | Homogenization |
Eudragit RS PO | 75% | 70% | 62% | - | Polymer |
Eudragit RL PO | - | - | - | 67% | Polymer |
Mg Stearate | 2.5% | 2.5% | 2.5% | - | Plasticizer |
Stearic acid | - | - | - | 4% | Plasticizer |
Components | 20% Flurbiprofen | 25% Flurbiprofen | 30% Flurbiprofen | 35% Flurbiprofen | Function |
---|---|---|---|---|---|
Flurbiprofen | 20% | 25% | 30% | 35% | API |
Talcum | 4% | 4% | 4% | 4% | Homogenization |
Eudragit RS PO | 72% | 67% | 62% | 57% | Polymer |
Stearic acid | 4% | 4% | 4% | 4% | Plasticizer |
Fraction | Particle Size Fraction |
---|---|
1 | 2 mm threads |
2 | 800 µm–2 mm |
3 | 630 µm–800 µm |
4 | 355 µm–630 µm |
5 | 250 µm–355 µm |
6 | 125 µm–250 µm |
7 | <125 µm |
Parameter | Value |
---|---|
Mobile phase and pH | ACN: H2O: TFA 58:42:0.1 pH 6.5 |
Flow rate | 1.0 mL/min |
Absorption wavelength | 248 nm |
Retention time | 8.8 min |
Correlation coefficient | 0.999 |
LOQ | 2.26 µg/mL |
Method reference | Nothnagel and Jung [40] |
Flurbiprofen % Loading (m/m) | Start | Middle | End | Mean | Rel.SD |
---|---|---|---|---|---|
E-RL extrudates | |||||
20% | |||||
1. Batch | 99.19% | 100.89% | 99.56% | 99.88% | 0.89% |
2. Batch | 101.63% | 99.74% | 100.24% | 100.54% | 0.97% |
25% | |||||
1. Batch | 101.53% | 100.65% | 100.22% | 100.80% | 0.67% |
2. Batch | 99.67% | 100.61% | 99.27% | 100.15% | 0.66% |
30% | |||||
1. Batch | 100.71% | 100.67% | 99.55% | 100.31% | 0.66% |
2. Batch | 100.25% | 99.29% | 99.47% | 99.67% | 0.68% |
35% | |||||
1. Batch | 100.41% | 99.81% | 99.19% | 99.81% | 0.61% |
2. Batch | 100.21% | 101.47% | 100.04% | 100.58% | 0.89% |
E-RS extrudates | |||||
20% | |||||
1. Batch | 101.92% | 99.51% | 99.18% | 100.21% | 1.49% |
2. Batch | 101.47% | 99.35% | 98.95% | 99.93% | 1.50% |
25% | |||||
1. Batch | 99.93% | 100.21% | 101.73% | 100.63% | 0.97% |
2. Batch | 100.17% | 101.09% | 98.63% | 100.64% | 0.65% |
30% | |||||
1. Batch | 99.43% | 99.21% | 97.97% | 98.87% | 0.80% |
2. Batch | 99.88% | 100.98% | 99.89% | 100.44% | 0.77% |
35% | |||||
1. Batch | 101.60% | 99.76% | 98.84% | 100.07% | 1.41% |
2. Batch | 99.39% | 101.74% | 99.53% | 100.57% | 1.65% |
Burst Release from the Fractionated Eudragit RL Extrudates at 25% (/m/m) Drug Load | |||||||
---|---|---|---|---|---|---|---|
Fractions | <125 µm | 125–250 µm | 250–355 µm | 355–630 µm | 630–800 µm | 800 µm–2 mm | 2 mm Threads |
Drug release (%) at 15 min | 20.10 | 20.04 | 11.46 | 8.28 | 5.58 | 4.64 | 0.96 |
Drug release (%) at 720 min | 84.90 | 83.14 | 81.01 | 58.57 | 43.87 | 21.18 | 6.30 |
Burst Release in % | 23.6 | 24.1 | 14.1 | 14.1 | 12.7 | 21.9 | 15.2 |
Burst release from the fractionated Eudragit RS extrudates at 25% (/m/m) drug load | |||||||
Drug release (%) at 15 min | 16.92 | 15.27 | 7.34 | 5.26 | 3.26 | 2.66 | 1.98 |
Drug release (%) at 720 min | 62.26 | 58.09 | 42.38 | 29.06 | 22.13 | 15.67 | 4.59 |
Burst Release in % | 26.8 | 26.2 | 17.3 | 18.1 | 14.7 | 16.9 | 43.1 |
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Mansuroglu, Y.; Dressman, J. Factors That Influence Sustained Release from Hot-Melt Extrudates. Pharmaceutics 2023, 15, 1996. https://doi.org/10.3390/pharmaceutics15071996
Mansuroglu Y, Dressman J. Factors That Influence Sustained Release from Hot-Melt Extrudates. Pharmaceutics. 2023; 15(7):1996. https://doi.org/10.3390/pharmaceutics15071996
Chicago/Turabian StyleMansuroglu, Yaser, and Jennifer Dressman. 2023. "Factors That Influence Sustained Release from Hot-Melt Extrudates" Pharmaceutics 15, no. 7: 1996. https://doi.org/10.3390/pharmaceutics15071996
APA StyleMansuroglu, Y., & Dressman, J. (2023). Factors That Influence Sustained Release from Hot-Melt Extrudates. Pharmaceutics, 15(7), 1996. https://doi.org/10.3390/pharmaceutics15071996