Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation and Optimisation of Thermoresponsive Gel Formulations
2.3. Fourier Transform Infra-Red Spectroscopy (FTIR)
2.4. Mechanical Properties
2.4.1. Gel Strength
2.4.2. Injectability
2.5. Rheological Properties
2.5.1. Frequency Sweep
2.5.2. Flow Sweep
2.6. Development and Validation of an Analytical Method for the Determination of BH
2.7. In Vitro Drug Release Studies
2.8. Mathematical Modelling of the Release Profiles
2.9. Statistical Analysis of Data
3. Results and Discussion
3.1. Formulation Preparation and Optimisation for Sol-To-Gel Transition Temperature
3.2. Fourier Transform Infra-Red (FTIR) Spectroscopy
3.3. Mechanical Properties
3.3.1. Gel Hardness and Strength
3.3.2. Injectability
3.4. Rheological Analysis
3.4.1. Frequency Sweep
3.4.2. Flow Sweep Analysis
3.5. Analytical Method Development and Validation
3.6. In Vitro Drug Release and Kinetic Modelling Studies
3.7. Mathematical Modelling
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Formulation Code | Composition | Total Poloxamers Conc. (wt.%) | PPO/PEO Ratio † | Sol-To-Gel Temperature (°C), Mean ± SD |
---|---|---|---|---|
F1 | P407 (23%), P188 (5.5%), H2O (71.5%) | 28.5 | 0.30 | 27.0 ± 0.00 |
F2 | P407 (20%), P188 (8.5%), H2O (71.5%) | 28.5 | 0.28 | 35.5 ± 0.33 |
F3 | P407 (19%), P188 (5.5%), H2O (75.5%) | 24.5 | 0.25 | 40.3 ± 0.47 |
F4 | P407 (21%), P188 (5.5%), H2O (73.5%) | 26.5 | 0.28 | 33.3 ± 0.47 |
F5 | P407 (25%), P188 (5.5%), H2O (69.5%) | 30.5 | 0.32 | * |
F6 | P407 (27%), P188 (5.5%), H2O (67.5%) | 33.5 | 0.34 | * |
F1SA | Sodium alginate (0.5 wt.%) + F1 | 28.5 | 0.30 | 26.0 ± 0.00 |
F1SA2 | Sodium alginate (0.75 wt.%) + F1 | 28.5 | 0.30 | 25.0 ± 0.33 |
F1SA3 | Sodium alginate (1.0 wt.%) + F1 | 28.5 | 0.30 | 23.0 ± 0.33 |
F1SA4 | Sodium alginate (0.5 wt.%) + Calcium chloride (0.5 wt.%) + F1 | 28.5 | 0.30 | ** |
F1CMC | Carboxy methylcellulose (0.35 wt.%) + F1 | 28.5 | 0.30 | 26.3 ± 0.33 |
F1CMC2 | Carboxy methylcellulose (0.75 wt.%) + F1 | 28.5 | 0.30 | 23.3 ± 0.33 |
F1MC | Methylcellulose (0.35 wt.%) + F1 | 28.5 | 0.30 | 25.6 ± 0.33 |
F1MC2 | Methylcellulose (0.5 wt.%) + F1 | 28.5 | 0.30 | 24.3 ± 0.67 |
F1MC3 | Methylcellulose (0.75 wt.%) + F1 | 28.5 | 0.30 | 22.3 ± 0.33 |
F1CH *** | Chitosan (MMW) (0.4 wt.%) + F1 | 28.5 | 0.30 | 25.6 ± 0.33 |
F1CH2 *** | Chitosan (MMW) (0.5 wt.%) + F1 | 28.5 | 0.30 | 25.6 ± 0.33 |
F1CH3 *** | Chitosan (MMW) (0.75 wt.%) + F1 | 28.5 | 0.30 | 24.3 ± 0.33 |
F1NaCl | Sodium chloride (0.4 wt.%) + F1 | 28.5 | 0.30 | 25.4 ± 0.33 |
F1NaCl2 | Sodium chloride (0.6 wt.%) + F1 | 28.5 | 0.30 | 24.3 ± 0.00 |
F1NaCl3 **** | Sodium chloride (0.9 wt.%) + F1 | 28.5 | 0.30 | 22.9 ± 0.00 |
Formulation Code | Sol-To-Gel Transition Temperature (°C) (Mean ± SD) | Sol-To-Gel Transition Time (S) (Mean ± SD) |
---|---|---|
F1 | 28.3 ± 0.33 | 90.0 ± 0.00 |
F2 | 36.3 ± 0.66 | 180.0 ± 4.08 |
F1SA | 27.3 ± 0.66 | 81.6 ± 2.35 |
F1MC | 26.6 ± 0.00 | 83.3 ± 2.35 |
F1CMC | 27.3 ± 0.00 | 85.0 ± 0.00 |
F1CH | 26.6 ± 0.33 | 95.0 ± 4.08 |
F1NaCl | 25.6 ± 0.33 | 30.0 ± 0.00 |
Formulation Code | Gel Hardness (g) Mean ± SD | Gel Strength (g. s) Mean ± SD | Maximum Force (g) Mean ± SD | Work Needed (g. m) Mean ± SD |
---|---|---|---|---|
F1 | 29.0 ± 3.4 | 124.8 ± 12.8 | 1688.0 ± 55.6 | 27.5 ± 1.7 |
F2 | 23.3 ± 1.1 | 102.3 ± 7.6 | 981.7 ± 32.0 | 15.9 ± 1.1 |
F1SA | 40.3 ± 5.5 | 168.5 ± 23.0 | 2598.9 ± 219.8 | 47.4 ± 4.4 |
F1MC | 39.8 ± 3.5 | 165.4 ± 13.6 | 2096.6 ± 90.5 | 37.1 ± 2.1 |
F1CMC | 40.2 ± 2.6 | 166.8 ± 10.2 | 2526.1 ± 143.8 | 46.4 ± 2.8 |
F1CH | 40.5 ± 4.6 | 166.2 ± 17.6 | 2448.1 ± 115.8 | 28.0 ± 1.1 |
F1NaCl | 50.75 ± 2.7 | 207.0 ± 18.4 | 1703.6 ± 89.3 | 29.2 ± 2.1 |
Parameters | Details |
---|---|
Column | Kinetex C18 ODS, 250 × 4.6 mm i.d., and 5 μm particle size |
Column temperature | Room temperature |
Mobile phase | Potassium phosphate buffer (pH 6.15–20 mM):acetonitrile:methanol (25:35:40) |
Flow rate | 1.0 mL/min |
Injection volume | 10 µL |
Detector | Diode array detector (DAD) |
Detection wavelength | 210 nm |
Formulation Code | Zero-Order | First-Order | Higuchi | Hixson–Crowell | Similarity Factor (f2) |
---|---|---|---|---|---|
R2 | |||||
F1 | 0.961 | 0.848 | 0.997 | 0.885 | NA |
F2 | 0.897 | 0.980 | 0.989 | 0.991 | 43 |
F1SA | 0.980 | 0.830 | 0.989 | 0.877 | 74 |
F1MC | 0.971 | 0.780 | 0.992 | 0.841 | 74 |
F1CMC | 0.977 | 0.847 | 0.992 | 0.889 | 80 |
F1CH | 0.913 | 0.894 | 0.994 | 0.920 | 51 |
F1NaCl | 0.949 | 0.848 | 0.993 | 0.891 | 69 |
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Abdeltawab, H.; Svirskis, D.; Hill, A.G.; Sharma, M. Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect. Gels 2022, 8, 484. https://doi.org/10.3390/gels8080484
Abdeltawab H, Svirskis D, Hill AG, Sharma M. Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect. Gels. 2022; 8(8):484. https://doi.org/10.3390/gels8080484
Chicago/Turabian StyleAbdeltawab, Hani, Darren Svirskis, Andrew G. Hill, and Manisha Sharma. 2022. "Increasing the Hydrophobic Component of Poloxamers and the Inclusion of Salt Extend the Release of Bupivacaine from Injectable In Situ Gels, While Common Polymer Additives Have Little Effect" Gels 8, no. 8: 484. https://doi.org/10.3390/gels8080484