Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods
Abstract
:1. Introduction
2. Results and Discussion
2.1. Antifungal Activity of CHD
2.2. Biofilm Recovery
2.3. Cytocompatibility
2.4. Characterisation of Powder Blends and Granules
2.4.1. Physical Properties of the Tablets
2.4.2. Swelling Index (SI)
2.4.3. Determination of Ex Vivo Residence Time
2.4.4. In Vitro Dissolution and Erosion Studies
2.5. Kinetics of Drug Release
2.6. Dissolution Efficiency (DE%)
3. Materials and Methods
3.1. Materials
3.2. Methods
3.2.1. Antifungal Assays
Minimum Inhibitory Concentration (MIC) and Minimum Biocidal Concentration (MBC)
C. albicans Biofilm Formation and Treatment
XTT Reduction Assay
Candida Survival after Treatment
3.2.2. Cytocompatibility
Cell Line and Culture Medium
Cytocompatibility Assay
3.2.3. Tablet Preparation
3.2.4. Powder Flow
Flowability (Mass Flow)
Compressibility Index
Melt Granulation
Tablet Pressing
3.2.5. Characterisation of Buccal Tablets
Friability
Tensile Strength
Swelling Index (SI)
Determination of Ex Vivo Residence Time
3.2.6. In Vitro Dissolution of CHD (Apparatus 1)
3.2.7. In Vitro Dissolution Using a Controlled Flow Rate (CFR)
3.2.8. Tablet Erosion E%
3.2.9. Dissolution Efficiency (DE%)
3.2.10. Kinetics of Drug Release
3.2.11. Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC)
3.2.12. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ingredients | S1 | S2 | S3 | S4 | M1 | M2 | M3 | M4 | X1 | X2 | X3 | X4 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Quantity mg/tab | ||||||||||||
CHD | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 |
P407 | 14 | 14 | 21 | 21 | 14 | 14 | 21 | 21 | 14 | 14 | 21 | 21 |
HPMC | 14 | 14 | 7 | 7 | 14 | 14 | 7 | 7 | 14 | 14 | 7 | 7 |
Sorbitol | 7 | 14 | 7 | 14 | - | - | - | - | - | - | - | - |
Mannitol | - | - | - | - | 7 | 14 | 7 | 14 | - | - | - | - |
Xylitol | - | - | - | - | - | - | - | - | 7 | 14 | 7 | 14 |
Weight | 37.5 | 44.5 | 37.5 | 44.5 | 37.5 | 44.5 | 37.5 | 44.5 | 37.5 | 44.5 | 37.5 | 44.5 |
Ratio (code) P407/HPMC/Polyol | 2:2:1 | 2:2:2 | 3:1:1 | 3:1:2 | 2:2:1 | 2:2:2 | 3:1:1 | 3:1:2 | 2:2:1 | 2:2:2 | 3:1:1 | 3:1:2 |
Formulation | Powder Blends | Granules | |||
---|---|---|---|---|---|
CI | Flow g/s | ||||
M1 | 30.81 ± 0.87 | p | 20.72 ± 0.61 | F | 4.73 ± 0.12 |
M2 | 37.20 ± 0.073 | VP | 20.57 ± 2.05 | F | 4.73 ± 0.12 |
M3 | 40.07 ± 0.66 | VVP | 12.50 ± 0.00 | G | 6.30 ± 0.00 |
M4 | 29.60 ± 0.37 | p | 11.81 ± 0.16 | G | 6.30 ± 0.00 |
X1 | 39.11 ± 1.32 | VVP | 20.86 ± 1.04 | F | 4.43 ± 0.15 |
X2 | 34.97 ± 4.23 | VP | 22.72 ± 1.09 | PA | 4.53 ± 0.12 |
X3 | 35.43 ± 3.81 | VP | 21.79 ± 1.43 | PA | 4.67 ± 0.23 |
X4 | 39.47 ± 2.70 | VVP | 21.81 ± 1.42 | PA | 6.00 ± 0.30 |
S1 | 39.50 ± 2.09 | VVP | 22.76 ± 1.05 | PA | 4.53 ± 0.15 |
S2 | 39.87 ± 1.66 | VVP | 22.32 ± 1.74 | PA | 4.80 ± 0.20 |
S3 | 39.32 ± 1.65 | VVP | 27.46 ± 1.37 | p | 6.83 ± 0.23 |
S4 | 41.55 ± 3.57 | VVP | 22.88 ± 1.26 | PA | 6.10 ± 0.00 |
Tensile Strength (MPa) n = 10 ± SD | Friability (%) | |
---|---|---|
S1 | 1.03 ±0.29 | 0.00 |
S2 | 0.80 ± 0.23 | 0.07 |
S3 | 0.90 ± 0.28 | 0.17 |
S4 | 0.85 ± 0.14 | 0.01 |
M1 | 0.63 ± 0.35 | 0.19 |
M2 | 0.94 ± 0.16 | 0.08 |
M3 | 0.96 ± 0.22 | 0.33 |
M4 | 0.88 ± 0.18 | 0.26 |
X1 | 0.37 ± 0.06 | 0.26 |
X2 | 0.67 ± 0.11 | 0.10 |
X3 | 0.56 ± 0.17 | 0.23 |
X4 | 0.74 ± 0.21 | 0.08 |
Formulations | % E (2 h) | % CHD Release (2 h) | Paired t Test |
---|---|---|---|
S1 | 36.87 ± 5.88 | 35.57 ± 0.76 | No significant difference p > 0.5 |
S2 | 39.70 ± 9.04 | 33.87 ± 4.16 | |
S3 | 70.84 ± 10.17 | 76.14 ± 2.52 | |
S4 | 88.15 ± 2.62 | 87.18 ± 2.99 | |
M1 | 28.43 ± 3.12 | 30.97 ± 4.58 | |
M2 | 28.86 ± 1.69 | 30.92 ± 2.92 | |
M3 | 69.50 ± 5.65 | 68.41 ± 3.40 | |
M4 | 84.63 ± 4.07 | 89.81 ± 1.22 | |
X1 | 30.41 ± 5.25 | 32.14 ± 2.35 | |
X2 | 36.44 ± 2.54 | 32.31 ± 1.00 | |
X3 | 70.41 ± 1.67 | 69.35 ± 2.03 | |
X4 | 87.21 ± 5.67 | 88.05 ± 3.26 |
ZERO | KP | HP | |||||||
---|---|---|---|---|---|---|---|---|---|
R2 | MSC | R2 | MSC | n | R2 | MSC | n | ||
Apparatus 1 | S1 | 0.978 | 3.3 | 0.994 | 4.6 | 0.750 | 0.992 | 181.8 | |
S2 | 0.992 | 4.3 | 0.995 | 4.2 | 0.848 | 0.997 | 4.6 | 2.2 | |
S3 | 0.979 | 3.4 | 0.998 | 4.6 | 0.708 | 0.991 | 248.6 | ||
S4 | 0.985 | 3.6 | 0.995 | 4.7 | 0.822 | 0.996 | 4.9 | 2 | |
M1 | 0.988 | 4.1 | 0.995 | 4.4 | 0.856 | 0.996 | 6.8 | ||
M2 | 0.975 | 3.2 | 0.985 | 3.4 | 0.819 | 0.991 | 291.1 | ||
M3 | 0.996 | 5.1 | 0.992 | 4.4 | 1.047 | 0.997 | 5.5 | 1.1 | |
M4 | 0.993 | 4.2 | 0.994 | 4.2 | 0.825 | 0.993 | 4.4 | 1.4 | |
X1 | 0.970 | 2.9 | 0.997 | 5.0 | 0.694 | 0.983 | 1344.8 | ||
X2 | 0.980 | 3.4 | 0.991 | 3.9 | 0.826 | 0.995 | 99.5 | ||
X3 | 0.988 | 3.9 | 0.991 | 3.9 | 1.058 | 0.996 | 5.1 | 1.7 | |
X4 | 0.992 | 4.3 | 0.995 | 4.5 | 0.815 | 0.995 | 4.8 | 1.6 | |
CFR 1 mL/min | S1 | 0.984 | 3.9 | 0.998 | 5.7 | 0.756 | 0.980 | 425.7 | |
S2 | 0.975 | 3.1 | 0.993 | 4.3 | 0.677 | 0.951 | 605.6 | ||
S3 | 0.998 | 5.9 | 0.999 | 6.9 | 0.941 | 0.998 | 6.0 | 1.2 | |
S4 | 0.998 | 5.9 | 0.998 | 5.4 | 0.992 | 0.998 | 5.8 | 1.0 | |
M1 | 0.991 | 4.2 | 0.999 | 6.9 | 0.783 | 0.990 | 671.8 | ||
M2 | 0.992 | 4.6 | 0.998 | 5.6 | 0.813 | 0.989 | 177.3 | ||
M3 | 0.998 | 6.0 | 1.000 | 7.7 | 0.895 | 0.999 | 6.2 | 1.4 | |
M4 | 0.999 | 6.4 | 0.999 | 5.6 | 0.962 | 0.999 | 6.5 | 1.1 | |
X1 | 0.988 | 3.9 | 0.999 | 6.7 | 0.766 | 0.988 | 495.6 | ||
X2 | 0.992 | 4.2 | 0.996 | 4.7 | 0.792 | 0.986 | 438.6 | ||
X3 | 0.998 | 6.0 | 0.999 | 6.6 | 0.901 | 0.998 | 6.0 | 1.3 | |
X4 | 0.999 | 6.6 | 0.999 | 6.4 | 0.956 | 0.999 | 6.5 | 1.0 |
Formulations | Apparatus I | CFR |
---|---|---|
S1 | 41.12 ± 2.46 | 20.25 ± 1.48 |
S2 | 39.12 ± 2.72 | 19.54 ± 3.46 |
S3 | 47.34 ± 0.73 | 38.78 ± 2.06 |
S4 | 48.89 ± 1.11 | 44.44 ± 1.92 |
M1 | 38.02 ± 2.49 | 17.19 ± 2.71 |
M2 | 36.85 ± 1.30 | 16.94 ± 2.39 |
M3 | 43.48 ± 0.63 | 35.31 ± 2.39 |
M4 | 49.03 ± 2.82 | 46.34 ± 0.54 |
X1 | 42.10 ± 0.46 | 18.16 ± 1.57 |
X2 | 37.19 ± 1.68 | 17.57 ± 0.43 |
X3 | 41.52 ± 2.79 | 35.74 ± 0.68 |
X4 | 51.40 ± 0.46 | 44.55 ± 2.34 |
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Al-Ani, E.; Hill, D.; Doudin, K. Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods. Pharmaceuticals 2021, 14, 493. https://doi.org/10.3390/ph14060493
Al-Ani E, Hill D, Doudin K. Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods. Pharmaceuticals. 2021; 14(6):493. https://doi.org/10.3390/ph14060493
Chicago/Turabian StyleAl-Ani, Enas, David Hill, and Khalid Doudin. 2021. "Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods" Pharmaceuticals 14, no. 6: 493. https://doi.org/10.3390/ph14060493
APA StyleAl-Ani, E., Hill, D., & Doudin, K. (2021). Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods. Pharmaceuticals, 14(6), 493. https://doi.org/10.3390/ph14060493