Hot-Melt Extrusion-Based Dexamethasone–PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials for Implant Manufacture
2.2. Material for LC-MS/MS Analysis
3. Methods—Implant Manufacture
3.1. Implant Formulations
3.2. Implant Manufacture by Hot-Melt Extrusion (HME)
3.3. Methods—Physicochemical Characterization
3.3.1. Implant Dexamethasone Content Determined by HPLC
3.3.2. Thermal Analysis—Using Differential Scanning Calorimetry (DSC)
3.4. Methods—Physicomechanical Characterization
3.4.1. Melt Viscosity
3.4.2. Influence of Humidity
Three-Point Bend (TPB) Tests Using a Texture Analyzer
Moisture Adsorption of Implants under High Relative Humidity
3.5. Methods—Surface Morphological Properties
3.5.1. Atomic Force Microscopy (AFM)
3.5.2. Polarized Light Microscopy (PLM) on Implant Films
3.5.3. Scanning Electron Microscopy (SEM)
3.5.4. Powder X-ray Diffraction (XRD) Analysis
3.6. Methods—In Vitro Release Testing
3.6.1. Large-Volume (100 mL) In Vitro Release Studies
3.6.2. HPLC-ESI+-MS/MS Detection and Quantification of Dexamethasone Release
3.6.3. Degradation Rate Constant and Concentration Correction in Phosphate-Buffered Saline Solution (PBS pH 7.4)
4. Results and Discussion
4.1. Dexamethasone Implant Manufacturing
4.2. Physiochemical Characterizations
4.2.1. Implant Dexamethasone Content Determined by HPLC
4.2.2. Thermal Analysis—Glass Transition Temperature (Tg) for Implants and Formulation Components Using Differential Scanning Calorimetry (DSC)
4.3. Physicomechanical Characterizations
4.3.1. Melt Viscosity of Implant Compositions
4.3.2. Three-Point Bend (TPB) Results
Influence of Humidity on Moisture Adsorption and TPB Mechanical Properties
4.4. Surface Morphological Properties
4.4.1. Surface Roughness of Dexamethasone-Loaded Implants by AFM
4.4.2. Crystalline Structure of Implants with/without Dexamethasone Based on PLM and XRD
4.4.3. Scanning Electron Microscopy (SEM) Imaging of HME Implants
4.5. In Vitro Dexamethasone Release Studies
4.5.1. In Vitro Dexamethasone Release Testing
4.5.2. Correlation of Implant Physicomechanical Properties with Dexamethasone Release
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Formulations | Theoretical Release Characteristic | Dexamethasone (g) | PLGA–Acid End-Capped (g) | PLGA–Ester End-Capped (g) |
---|---|---|---|---|
HME-1 | Fast | 2 | 8.0 | 0 |
HME-2 | Intermediate | 2 | 6.4 | 1.6 |
HME-3 | Slow | 2 | 4.8 | 3.2 |
HME-4 | Fast | 0 | 10.0 | 0 |
HME-5 | Intermediate | 0 | 8.0 | 2.0 |
HME-6 | Slow | 0 | 6.0 | 4.0 |
Setting Description | Setting |
---|---|
Test Mode | Compression |
Test Speed | 0.1 mm/s |
Target Mode | Distance |
Gap Space | 1.00 cm (0.394 in) |
Stop Plot at | Target distance |
Distance | 5 mm |
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Ghaffari, A.; Matter, B.A.; Hartman, R.R.; Bourne, D.W.A.; Wang, Y.; Choi, S.; Kompella, U.B. Hot-Melt Extrusion-Based Dexamethasone–PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation. Pharmaceutics 2024, 16, 895. https://doi.org/10.3390/pharmaceutics16070895
Ghaffari A, Matter BA, Hartman RR, Bourne DWA, Wang Y, Choi S, Kompella UB. Hot-Melt Extrusion-Based Dexamethasone–PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation. Pharmaceutics. 2024; 16(7):895. https://doi.org/10.3390/pharmaceutics16070895
Chicago/Turabian StyleGhaffari, Alireza (Allen), Brock A. Matter, Rachel R. Hartman, David W. A. Bourne, Yan Wang, Stephanie Choi, and Uday B. Kompella. 2024. "Hot-Melt Extrusion-Based Dexamethasone–PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation" Pharmaceutics 16, no. 7: 895. https://doi.org/10.3390/pharmaceutics16070895
APA StyleGhaffari, A., Matter, B. A., Hartman, R. R., Bourne, D. W. A., Wang, Y., Choi, S., & Kompella, U. B. (2024). Hot-Melt Extrusion-Based Dexamethasone–PLGA Implants: Physicochemical, Physicomechanical, and Surface Morphological Properties and In Vitro Release Corrected for Drug Degradation. Pharmaceutics, 16(7), 895. https://doi.org/10.3390/pharmaceutics16070895