Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Screening Tests
2.2.2. HPLC Analysis
2.2.3. Preparation of Nanoemulsion-Ultrasonication
2.2.4. Characterization of Emulsion
2.2.5. Emulsion stability
2.2.6. Preparation of Self Emulsifying Pellets (SEPs)
2.2.7. Chemical Stability
2.2.8. Characterization of Self Emulsifying Pellets
Pycnometric and tap densities
Particle Size and Shape Analysis
2.2.9. Reconstitution of Emulsions from Pellets
2.2.10. Preparation of Self-Emulsifying Tablets (SETs)
2.2.11. Evaluation of SETs
2.2.12. In Vitro Release
2.2.13. Permeability experiments-Caco-2 Cells
2.2.14. Cytotoxicity Test
3. Results and discussion
3.1. Screening Studies
3.2. Preparation
3.3. Characterization of Microemulsions
3.3.1. Rheology
3.3.2. Droplet Size and Zeta Potential
3.3.3. Structural Changes of Emulsions Followed by Light Scattering
3.3.4. Robustness to Dilution
3.4. Composition of Self-Emulsifying Pellets (SEPs)
3.5. Particle Size, Shape, and Packing of SEPs
3.6. Friability of SEPs
3.7. Reconstitution of Emulsions from SEPs
3.8. Self-Emulsifying Tablets
3.9. Disintegration of Tablets into Pellets and In Vitro Release
3.10. Chemical and Physical Stability
3.11. Permeability Study with Caco-2 cell Culture
3.12. Cytotoxicity
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Ingredient | Solubility (mg/mL) (±SD) |
---|---|
Corn oil | 7.71 ± 0.05 |
Oleic acid | 27.40 ± 0.03 |
Refined castor oil | 1.53 ± 0.02 |
Labrofil M 2125 | 4.47 ± 0.04 |
Labrafil 1944 | 0.01 ± 0.04 |
Tween 20 | 263.5 ± 0.09 |
Tween 80 | 13.50 ± 0.02 |
Span 80 | 47.47 ± 0.03 |
PEG 200 | 45.98 ± 0.03 |
Transcutol | 6.74 ± 0.04 |
Labrasol | 17.30 ± 0.18 |
Brij 30v | 44.73 ± 0.21 |
Brij 92v | 30.19 ± 0.04 |
Brij 96v | 3.38 ± 0.03 |
Ethanol | 0.04 ± 0.02 |
Isopropyl alcohol | 4.71 ± 0.06 |
N-methyl pyrrolidone | 110.55 ± 0.03 |
Distilled water | 0.01 ± 0.05 |
pH: 1.2 | 0.004 ± 0.02 |
pH: 4.6 | 0.02 ± 0.01 |
pH: 6.8 | 0.602 ± 0.03 |
Ingredient | Composition |
---|---|
Drug | 1.2 (2.7%) |
Aerosil 200 | 14.0 (31.1%) |
Avicel 101 | 6.0 (13.3%) |
Oleic acid | 14.4 (32.0%) |
Tween 20 | 5.7 (12.6%) |
Span 80 | 2.8 (6.2%) |
N-methyl pyrrolidone | 0.96 (2.1%) |
Total weight | 45.0 (100%) |
Self-Emulsifying Pellets (SEPs) | Avicel 101 | Compression (MPa) |
---|---|---|
20 | 80 | 20 |
20 | 80 | 40 |
20 | 80 | 60 |
30 | 70 | 20 |
30 | 70 | 40 |
30 | 70 | 60 |
40 | 60 | 20 |
40 | 60 | 40 |
40 | 60 | 60 |
Property | Non-Sonicated | Sonicated |
---|---|---|
Droplet size | 1370 ± 23 | 320.7 ± 15 |
Viscosity (cP) | 249.5 | 68.5 |
Zeta potential (mV) | −7.05 ± 0.48 | −7.98 ± 0.35 |
Dispersion Medium | Dilution Level | Diameter (nm) | Coefficient of Variation (CV%) |
---|---|---|---|
pH 1.2 | 1:10 | 288.6 ± 1.5 | 19.3 |
pH 1.2 | 1:100 | 306.7 ± 1.0 | |
pH 1.2 | 1:1000 | 209.5 ± 1.5 | |
pH 1.2 | 1:1000/24 h | 210.9 ± 1.0 | |
pH 6.8 | 1:10 | 215.7 ± 1.5 | 21.6 |
pH 6.8 | 1:100 | 307.0 ± 1.3 | |
pH 6.8 | 1:1000 | 214.5 ± 1.0 | |
pH 6.8 | 1:1000/24 h | 285.9 ± 1.3 | |
Deionised water | 1:10 | 273.1 ± 2.6 | 22.8 |
Deionised water | 1:100 | 320.7 ± 1.5 | |
Deionised water | 1:1000 | 200.8 ±2.3 | |
Deionised water | 1:1000/24 h | 198.4 ± 1.8 |
Median Diameter (μm) | 1065 |
Shape index (eR) | 0.469 |
Circularity | 0.832 |
Pycnometric density | 1.31 ± 0.01 |
Bulk density | 0.72 ± 0.04 |
Tap density | 0.77 ± 0.02 |
Hausner ratio | 1.07 ± 0.01 |
Carr’s index | 6.46 ± 0.61 |
Friability (%) | 1.3 ± 0.05 |
Time 0 | Three Months | Six Months | ||||
---|---|---|---|---|---|---|
25 °C/60% | 40 °C/75% | 25 °C/60% | 40 °C/75% | 25 °C/60% | 40 °C/75% | |
Drug (%) | 106 ± 1.53 | 103 ± 1.35 | 104 ± 2.00 | 102 ± 1.87 | 102 ± 1.99 | 101 ± 1.47 |
Apparent Permeability Coefficient | Pefflux | Cytotoxicity | ||
---|---|---|---|---|
A→B | B→A | |||
AtrCa | 8.01 × 10−5 ± 5.56 × 10−6 | 1.59 × 10−4 ± 4.03 × 10−5 | 0.503 0.12 | 72% |
Self-emulsifying pellets | 6.16 × 10−4 ± 1.23 × 10−5 | 5.85 × 10−4 ± 5.67 × 10−6 | 1.046 0.02 | 88.9% |
Commercial Tablet | 4.87 × 10−4 ± 8.3 × 10−5 | 6.79 × 10−4 ± 5.37 × 10−5 | 0.718 0.15 | 89.9% |
Apparent Permeability Coefficient | Pefflux | ||
---|---|---|---|
A→B | B→A | ||
AtrCa - SEP | 0.005 | 0.000 | 0.002 |
AtrCa–Comm. tabl. | 0.000 | 0.000 | 0.096 |
SEP–Comm. Tabl. | 0.026 | 0.051 | 0.020 |
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Diril, M.; Karasulu, Y.; Toskas, M.; Nikolakakis, I. Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets. Processes 2019, 7, 365. https://doi.org/10.3390/pr7060365
Diril M, Karasulu Y, Toskas M, Nikolakakis I. Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets. Processes. 2019; 7(6):365. https://doi.org/10.3390/pr7060365
Chicago/Turabian StyleDiril, Mine, Yesim Karasulu, Miltiadis Toskas, and Ioannis Nikolakakis. 2019. "Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets" Processes 7, no. 6: 365. https://doi.org/10.3390/pr7060365
APA StyleDiril, M., Karasulu, Y., Toskas, M., & Nikolakakis, I. (2019). Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets. Processes, 7(6), 365. https://doi.org/10.3390/pr7060365