Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Fenofibrate Microparticles
2.2.1. SA-SD Process
2.2.2. Box–Behnken Design (BBD)
2.2.3. Preparation of Fenofibrate Microcomposite Particles under Optimized Conditions
2.2.4. Conventional Spray-Drying (SD) Process
2.3. Physicochemical Characterization of Fenofibrate Microparticles
2.3.1. Particle Size Analysis
2.3.2. Powder X-ray Diffraction (PXRD)
2.3.3. Differential Scanning Calorimetry (DSC)
2.3.4. Scanning Electron Microscopy (SEM)
2.3.5. X-ray Photoelectron Spectroscopy (XPS)
2.3.6. Zeta Potential Measurement
2.3.7. Contact Angle Measurement
2.3.8. Dissolution Test
2.4. In Vivo Studies Using Sprague–Dawley Rats
2.4.1. Pharmacokinetic (PK) Study
2.4.2. Pharmacodynamic (PD) Studies in Sprague–Dawley Rats
3. Results and Discussion
3.1. Optimization of Fenofibrate Microparticle Formation Using Box–Behnken Design (BBD)
3.2. Physicochemical Characterization of Fenofibrate-Additive Microcomposite Particles
3.3. Pharmacokinetic (PK) Profile of Fenofibrate Microparticles in Sprague–Dawley Rats
3.4. Pharmacodynamic (PD) Therapeutic Efficacy in Sprague–Dawley Rats
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Formula | Surface-Active Additive | Content (w/w, %) of Additive in Solid Formula | Particle Formation Process |
---|---|---|---|
SS1 | Sucroester 15 | 5 | Supercritical assisted spray-drying (SA-SD) |
SS2 | TPGS | 5 | SA-SD |
SS3 | Myrj 52 | 5 | SA-SD |
SD1 | Sucroester 15 | 5 | Spray-drying (SD) |
SD2 | TPGS | 5 | SD |
SD3 | Myrj 52 | 5 | SD |
Formula | Mean Particle Size (μm) | SPAN a | Zeta Potential (mV) | Contact Angle (°) | |||
---|---|---|---|---|---|---|---|
Raw b | 23.80 | ±0.64 | 4.25 | −17.12 | ±1.13 | 80.38 | ±2.83 |
SS1 | 1.86 | ±0.21 | 1.27 | −22.56 | ±1.74 | 57.42 | ±4.12 |
SS2 | 2.17 | ±0.12 | 1.18 | −9.87 | ±1.35 | 58.78 | ±3.37 |
SS3 | 2.04 | ±0.25 | 1.22 | −11.74 | ±2.03 | 60.01 | ±2.81 |
SD1 | 33.98 | ±1.21 | 3.84 | −31.29 | ±1.96 | 41.05 | ±3.24 |
SD2 | 43.76 | ±1.53 | 3.93 | −7.42 | ±2.14 | 42.17 | ±4.56 |
SD3 | 49.16 | ±1.37 | 3.60 | −6.39 | ±1.94 | 28.97 | ±3.89 |
Numbers of Atom | Atomic Concentration (%) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Substance | C | O | Cl | C1s | O1s | Cl2p | |||
Fenofibrate | 20 | 4 | 1 | 80.4 | ±0.8 | 15.0 | ±0.7 | 4.6 | ±0.4 |
Theory a | - | - | - | 80.0 | 16.0 | 4.0 | |||
Sucroester 15 | 28 | 12 | - | 70.3 | ±0.7 | 29.7 | ±0.5 | - | |
Theory a | - | - | - | 70.0 | 30.0 | - | |||
TPGS | 57 | 28 | - | 68.1 | ±0.9 | 31.9 | ±0.6 | - | |
Theory a | - | - | - | 67.1 | 32.9 | - | |||
Myrj 52 | 122 | 54 | - | 69.9 | ±0.7 | 20.1 | ±0.4 | - | |
Theory a | - | - | - | 69.3 | 30.7 | - |
Formula | Atomic Concentration (%) | Surface Coverage of Additive (%) | Surface Excess of Additive a | |||||
---|---|---|---|---|---|---|---|---|
C1s | O1s | Cl2p | ||||||
SS1 | 77.5 | ±0.9 | 16.8 | ±0.6 | 3.7 | ±0.6 | 8.3 | 1.7 |
SS2 | 78.7 | ±0.6 | 17.2 | ±0.4 | 3.6 | ±0.3 | 7.5 | 1.5 |
SS3 | 78.1 | ±0.5 | 16.7 | ±0.5 | 4.1 | ±0.7 | 6.5 | 1.3 |
SD1 | 77.7 | ±0.4 | 19.5 | ±0.7 | 2.8 | ±0.8 | 24.7 | 4.9 |
SD2 | 77.9 | ±0.8 | 19.7 | ±0.3 | 2.4 | ±0.9 | 20.8 | 4.2 |
SD3 | 77.2 | ±0.7 | 20.2 | ±0.6 | 2.6 | ±0.7 | 28.1 | 5.6 |
AUC0–12 h (μg∙h/mL) | Cmax (μg/mL) | Tmax (h) | ||||
---|---|---|---|---|---|---|
Unprocessed Fenofibrate | 139.1 | ±74.4 | 19.8 | ±10.1 | 3.5 | ±0.6 |
SS1 | 537.4 | ±90.1 | 77.8 | ±6.2 | 2.5 | ±0.6 |
SS2 | 519.0 | ±65.5 | 74.9 | ±14.3 | 2.8 | ±1.0 |
SS3 | 475.1 | ±96.8 | 70.2 | ±8.9 | 2.5 | ±0.6 |
SD1 | 129.8 | ±59.0 | 17.8 | ±5.3 | 3.5 | ±1.0 |
SD2 | 92.3 | ±56.6 | 11.8 | ±6.7 | 3.3 | ±0.6 |
SD3 | 89.2 | ±24.9 | 12.0 | ±3.6 | 3.5 | ±0.6 |
Phase I (After 24 h) | Phase II (After 48 h) | |||||||
---|---|---|---|---|---|---|---|---|
Group | Total Cholesterol (mg/dL) | Triglycerides (mg/dL) | Total Cholesterol (mg/dL) | Triglycerides (mg/dL) | ||||
Control | 70.4 | ±9.5 | 131.7 | ±6.7 | 68.9 | ±10.6 | 109.2 | ±4.9 |
Triton | 256.7 | ±9.0 | 370.1 | ±7.5 | 141.1 | ±6.2 | 221.1 | ±4.5 |
Unprocessed | 124.7 | ±24.5 (70.8) | 241.4 | ±3.7 (54.0) | 88.7 | ±9.2 (72.6) | 159.8 | ±7.1 (54.8) |
SS1 | 86.1 | ±8.6 (91.6) | 152.4 | ±2.5 (91.3) | 73.9 | ±4.0 (93.0) | 127.5 | ±3.9 (83.7) |
SS2 | 89.6 | ±10.8 (89.7) | 173.9 | ±10.5 (82.3) | 74.1 | ±5.9 (92.8) | 139.6 | ±12.2 (72.9) |
SS3 | 96.7 | ±4.7 (85.9) | 170.8 | ±4.0 (83.6) | 78.3 | ±9.2 (86.9) | 135.4 | ±3.3 (76.6) |
SD1 | 138.1 | ±1.3 (63.6) | 231.9 | ±5.3 (58.0) | 93.6 | ±9.8 (65.8) | 148.7 | ±5.8 (64.7) |
SD2 | 146.1 | ±2.3 (59.3) | 243.9 | ±4.1 (52.9) | 91.7 | ±14.0 (68.4) | 165.8 | ±7.6 (49.5) |
SD3 | 146.3 | ±23.8 (59.2) | 249.7 | ±6.4 (50.5) | 102.9 | ±8.5 (52.9) | 159.8 | ±5.1 (54.8) |
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Kim, J.-S.; Park, H.; Ha, E.-S.; Kang, K.-T.; Kim, M.-S.; Hwang, S.-J. Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process. Pharmaceutics 2021, 13, 2061. https://doi.org/10.3390/pharmaceutics13122061
Kim J-S, Park H, Ha E-S, Kang K-T, Kim M-S, Hwang S-J. Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process. Pharmaceutics. 2021; 13(12):2061. https://doi.org/10.3390/pharmaceutics13122061
Chicago/Turabian StyleKim, Jeong-Soo, Heejun Park, Eun-Sol Ha, Kyu-Tae Kang, Min-Soo Kim, and Sung-Joo Hwang. 2021. "Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process" Pharmaceutics 13, no. 12: 2061. https://doi.org/10.3390/pharmaceutics13122061
APA StyleKim, J.-S., Park, H., Ha, E.-S., Kang, K.-T., Kim, M.-S., & Hwang, S.-J. (2021). Preparation and Characterization of Fenofibrate Microparticles with Surface-Active Additives: Application of a Supercritical Fluid-Assisted Spray-Drying Process. Pharmaceutics, 13(12), 2061. https://doi.org/10.3390/pharmaceutics13122061