Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. The Binary System Obtaining Processes
Kneading Product
Preparation of the Inclusion Compounds Using Liquid-State Coprecipitation and Lyophilization Techniques
Preparation of Physical Mixtures
2.2.2. Physicochemical Characterization
2.2.3. Preformulation and Formulation Studies for Orodispersible Tablets Containing AML-HP-β-CD and AML-Me-β-CD Inclusion Complexes
Formulation of Direct Compression Blends
Materials for Direct Compression Preparation
The Pharmacotechnical Properties of the Direct Compression Powders
2.2.4. Development and Manufacturing of Orodispersible Tablets Containing AML-HP-β-CD and AML-Me-β-CD Inclusion Complexes
Formulation of the Orodispersible Tablets Containing AML-HP-β-CD and AML-Me-β-CD Inclusion Complexes
Manufacturing Process of Tablets for Oral Dispersion
2.2.5. Quality Assessment Parameters
In Vitro Disintegration Time
In Vitro Dissolution Studies
3. Results
3.1. Binary Systems Characterization
3.2. Characterization of the Inclusion Complexes
3.3. Preformulation and Formulation Studies for Orodispersible Tablets Containing AML-HP-β-CD and AML-Me-β-CD Inclusion Complexes
Particle Size Distribution
3.4. Quality Assessment of Orally Dispersible Tablets
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ingredients | Formulation/Amount (%) | |||||
---|---|---|---|---|---|---|
F1 | F2 | F3 | F4 | F5 | F6 | |
AML-HP-β-CD | 5.39 | 5.39 | 5.39 | - | - | - |
AML-Me-β-CD | - | - | - | 6.00 | 6.00 | 6.00 |
PROSOLV® SMCC HD 90-Silicified microcrystalline cellulose | 91.75 | - | - | 91.14 | - | - |
F-MELT® | - | 91.75 | - | - | 91.14 | - |
Ludiflash® | - | - | 91.75 | - | - | 91.14 |
EXPLOTAB®-Sodium starch glycolate | 1.86 | 1.86 | 1.86 | 1.86 | 1.86 | 1.86 |
LIGAMED® MF-2-V-Magnesium stearate | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 |
Ingredients | Quantity mg/Tablet | Role in Formulation | |||
---|---|---|---|---|---|
F7 (F1-30 kN) | F8 (F1-60 kN) | F9 (F4-30 kN) | F10 (F4-60 kN) | ||
Inclusion complex AML-HP-β-CD (1:1) | 18.87 | 18.87 | - | - | Active ingredient |
Inclusion complex AML-Me-β-CD (1:1) | - | - | 21.02 | 21.02 | Active ingredient |
PROSOLV® SMCC HD 90-Silicified microcrystalline cellulose | 321.13 | 321.13 | 318.98 | 318.98 | Filler Binder |
EXPLOTAB®-Sodium starch glycolate | 6.50 | 6.50 | 6.50 | 6.50 | Superdisintegrant |
LIGAMED® MF-2-V-Magnesium stearate | 3.50 | 3.50 | 3.50 | 3.50 | Lubricant |
TOTAL | 350.00 | 350.00 | 350.00 | 350.00 |
Sample | Process | Tonset/(°C) | Tmax/(°C) | Tend/(°C) | ΔH/(Jg−1) |
---|---|---|---|---|---|
AML | Dehydration | 82.1 | 105.9 | 109.7 | 21.7 |
Melting | 140.2 | 141.2 | 142.3 | 80.3 | |
HP-β-CD | Melting | 208.6 | 209.2 | 210.9 | 43.2 |
AML-HP-β-CD physical mixture | Dehydration | 101.9 | 102.2 | 104.1 | 0.9 |
Melting | 131.7 | 133.6 | 135.1 | 13.3 | |
Decomposition | 275.4 | 285.2 | 287.1 | 11.8 | |
AML-HP-β-CD kneading | Dehydration | 116.2 | 118.3 | 120.0 | 7.7 |
Melting | 136.5 | 137.1 | 138.2 | 6.2 | |
Decomposition | 291.2 | 291.9 | 292.9 | 39.0 | |
AML-HP-β-CD coprecipitation | Melting | 140.5 | 141.6 | 142.4 | 78.8 |
AML-HP-β-CD lyophilization | Melting | 126.3 | 130.5 | 131.3 | 1.3 |
Decomposition | 265.4 | 266.5 | 268.5 | 9.5 | |
Me-β-CD | Melting | 209.9 | 210.3 | 211.1 | 0.19 |
Decomposition | 285.5 | 286.0 | 286.8 | 13.9 | |
287.3 | 289.1 | 295.0 | 21.8 | ||
AML-Me-β-CD physical mixture | Melting | 129.1 | 133.6 | 139.0 | 6.8 |
AML-Me-β-CD kneading | Dehydration | 66.0 | 66.4 | 66.8 | 0.5 |
AML-Me-β-CD coprecipitation | Melting | 139.0 | 140.1 | 141.2 | 72.7 |
Decomposition | 235.6 | 263.9 | 293.6 | 41.7 | |
AML-Me-β-CD lyophilization | Dehydration | 72.9 | 76.0 | 80.7 | 3.3 |
Decomposition | 227.9 | 250.4 | 250.4 | 1.1 |
Parameter | Formulation Code | |||||
---|---|---|---|---|---|---|
F1 | F2 | F3 | F4 | F5 | F6 | |
Moisture content (%) | 3.52 ± 1.31 | 6.29 ± 1.47 | 7.11 ± 2.33 | 4.03 ± 1.57 | 6.83 ± 2.12 | 7.35 ± 1.78 |
Flow time (s) * | 9.3 ± 1.06 | 12.8 ± 1.17 | 13.1 ± 1.69 | 10.2 ± 1.31 | 16.5 ± 1.95 | 17.2 ± 2.36 |
Angle of repose (θ degrees) * | 26.42 ± 1.26 | 31.19 ± 2.10 | 30.89 ± 2.85 | 27.37 ± 1.48 | 35.12 ± 2.61 | 36.44 ± 2.94 |
Flow rate (g/s) * | 6.451 | 4.687 | 4.580 | 5.882 | 3.636 | 3.488 |
Bulk density (g/mL) | 0.512 | 0.577 | 0.525 | 0.534 | 0.563 | 0.582 |
Tapped density (g/mL) | 0.585 | 0.682 | 0.679 | 0.621 | 0.681 | 0.723 |
Carr Index (CI) (%) | 12.48 | 15.4 | 22.68 | 14.01 | 17.33 | 19.50 |
Hausner’s ratio (HR) | 1.14 | 1.18 | 1.29 | 1.12 | 1.20 | 1.24 |
Characteristics | Formulation Code | |||
---|---|---|---|---|
F7 | F8 | F9 | F10 | |
Thickness (mm) | 4.02 ± 0.44 | 4.00 ± 1.12 | 4.08 ± 0.78 | 4.05 ± 0.95 |
Diameter (mm) | 10 ± 0.31 | 10 ± 0.63 | 10 ± 0.11 | 10 ± 0.59 |
Mass uniformity | 349 ± 1.95 | 347 ± 2.46 | 350 ± 1.78 | 348 ± 3.65 |
Hardness (N) | 44 ± 3.71 | 57.8 ± 3.55 | 42.2 ± 3.14 | 61.2 ± 4.29 |
Friability (%) | 0.03 ± 0.09 | 0.05 ± 0.12 | 0.12 ± 0.25 | 0.34 ± 0.33 |
In vitro disintegration time–in water medium (seconds) | 14 ± 1.24 | 21 ± 2.71 | 13 ± 1.15 | 19 ± 1.97 |
In vitro disintegration time–in simulated saliva medium (seconds) | 12 ± 3.55 | 16 ± 2.81 | 11 ± 3.22 | 18 ± 4.55 |
In vitro dissolution rate–in acidic medium, after 30 min (%) | 98.76 ± 1.45 | 96.31 ± 2.08 | 98.11 ± 1.35 | 97.13 ± 1.92 |
In vitro dissolution rate–in simulated saliva medium, after 30 min (%) | 90.18 ± 1.26 | 88.12 ± 1.84 | 89.84 ± 1.12 | 85.15 ± 2.23 |
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Novac, M.; Musuc, A.M.; Ozon, E.A.; Sarbu, I.; Mitu, M.A.; Rusu, A.; Petrescu, S.; Atkinson, I.; Gheorghe, D.; Lupuliasa, D. Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin. Materials 2022, 15, 5217. https://doi.org/10.3390/ma15155217
Novac M, Musuc AM, Ozon EA, Sarbu I, Mitu MA, Rusu A, Petrescu S, Atkinson I, Gheorghe D, Lupuliasa D. Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin. Materials. 2022; 15(15):5217. https://doi.org/10.3390/ma15155217
Chicago/Turabian StyleNovac, Marian, Adina Magdalena Musuc, Emma Adriana Ozon, Iulian Sarbu, Mirela Adriana Mitu, Adriana Rusu, Simona Petrescu, Irina Atkinson, Daniela Gheorghe, and Dumitru Lupuliasa. 2022. "Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin" Materials 15, no. 15: 5217. https://doi.org/10.3390/ma15155217