Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Solubility Determination
2.3. Suspensions
2.3.1. Preparation
2.3.2. Characterization
2.4. Small-Scale Dissolution Measurements
2.4.1. Standard Curve
2.4.2. Dissolution from Controlled Suspensions
2.4.3. Dissolution from Discs
2.4.4. Calculation of the Intrinsic Dissolution Rate (IDR)
2.5. Statistics and Physicochemical Analysis
3. Results and Discussion
3.1. Rapid Preparation of Controlled Suspensions by Ultrasonication and their Characterization
3.2. Dissolution Profiling
3.3. Impact of Physicochemical Properties on IDR
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Structure | Mw* g/mol | A/B/N | pKa | logP | Tm °C | ΔHf J/g | Crystalline Form As-Received† | Food ‡ |
---|---|---|---|---|---|---|---|---|---|
Astemizole | | 458.6 | B | 8.1 | 5.9 | 174 [22] | 111 [22] | (ZENREP)* | - |
Bezafibrate | | 361.9 | A | 3.5 | 4.0 | 182 | 145 | α form [23] | + |
Carvedilol | | 406.5 | B | 8.1 | 4.0 | 117 [24] | 120 [24] | form II [25] | + |
Cinnarizine | | 368.6 | B | 7.4 | 5.3 | 117 | 118 | ([26]) | + |
Danazol | | 337.5 | N | - | 3.6 | 226 | 92 | ([27]) | +/- |
Dipyridamole | | 504.7 | B | 6.8; 3.6 | 2.2 | 166 [28] | 56 [28] | form II [29] | + |
Ethinylestradiol | | 296.4 | N | - | 3.6 | 183 [30] | 89 [31] | hemihydrate [31] | +/- |
Felodipine | | 384.3 | N | - | 4.8 | 142 | 76 | form I [32] | +/- |
Fenofibrate | | 360.9 | N | - | 5.3 | 79 | 98 | form I [33] | + |
Fenofibric acid | | 318.8 | A | 3.5 | 4.0 | 181 [34] | - | (QANHUJ)* | +/- |
Griseofulvin | | 352.8 | N | - | 2.5 | 215 | 122 | ([35]) | + |
Indomethacin | | 357.8 | A | 4.1 | 3.8 | 160 [22] | 106 [22] | γ form [36] | +/- |
Mefenamic acid | | 241.3 | A | 4.0 | 4.9 | 230 [37] | 158 [37] | form I [38] | + |
Naproxen | | 230.3 | A | 4.5 | 3.3 | 156 [22] | 149 [22] | form I [39] | +/- |
Noscapine | | 413.4 | B | 6.1 | 2.8 | 176 [40] | - | ([40]) | - |
Progesterone | | 314.5 | N | - | 3.9 | 129 [41] | 89 [42] | form I [43] | + |
Tadalafil | | 389.4 | N | - | 1.6 | 295 [44] | 113 [44] | form I [45] | +/- |
Tolfenamic acid | | 261.7 | A | 4.2 | 5.3 | 212 | 143 | form I [46] | n/a |
Component | FaSSIF-V1 | FeSSIF-V1 | FaSSIF-V2 | FeSSIF-V2 | |
---|---|---|---|---|---|
Taurocholate | mM | 3 | 15 | 3 | 10 |
Phospholipids | 0.75 | 3.75 | 0.2 | 2 | |
Sodium | 148 | 319 | 106 | 218 | |
Chloride | 106 | 203 | 69 | 125 | |
Phosphate | 29 | ||||
Acetic acid | 144 | ||||
Maleic acid | 19 | 55 | |||
Oleate | 0.8 | ||||
Glycerol monleate | 5 | ||||
pH | 6.5 | 5 | 6.5 | 5.8 | |
Hydrodynamic diameter | nm | 71 | 8 | 32 | 35 |
Compound | SFaSSIF-V1 μg/mL | SFeSSIF-V1 μg/mL | D/S | IDRFaSSIF-V1 μg/min/cm2 | IDRFeSSIF-V1 μg/min/c2 | IDRFaSSIF-V2 μg/min/cm2 | IDRFeSSIF-V2 μg/min/cm2 |
---|---|---|---|---|---|---|---|
Astemizole | 97.9 ± 2.1 [15] | 182 ± 1 [15] | S | 8.6 ± 0.4 | 67.5 ± 14 | 2.0 ± 0.2 | - |
Bezafibrate | 91.0 ± 8.9 † | 105.7 ‡ | S | 32.7 ± 3.9 | 3.1 ± 0.04 | - | - |
Carvedilol | 55.9 ± 1.0 [15] | 305 ± 2 [15] | S | 2.9 ± 0.5 | 11.7 ± 0.9 | 1.5 ± 0.2 | 13.6 ± 0.6 |
Cinnarizine | 11.1 ± 1.2 [7] | 112 ± 2 [15] | S | 0.3 ± 0.01 | 1.8 ± 0.07 | - | - |
Danazol | 8.4 ± 0.7 [15] | 28.8 ± 0.4 [15] | S | 0.14 ± 0.02 | 3.9 ± 0.4 | - | - |
Dipyridamole | 11.1 ± 3.0 [48] | 148.9 ± 19.7 [48] | S | 0.5 ± 0.05 | 7.8 ± 2.6 | 0.5 ± 0.03 | 1.7 ± 0.3 |
Ethinylestradiol | 18.7 ± 1.3 * | - | D | 3.2 ±0.1 | 22.1 ±3.1 | 6.6 ± 0.8 | - |
Felodipine | 31.8 ± 1.7 [7] | 44.9 ± 9.2 [48] | S | 0.8 ± 0.4 | 1.5 ± 0.06 | 0.6 ± 0.2 | 1.5 ± 0.2 |
Fenofibrate | 12.2 ± 0.3 [7] | 40.4 ± 2.9 [49] | S | 0.04 ± 0.002 | 0.2 ± 0.008 | 0.05 ± 0.001 | 2.7 ± 0.3 |
Fenofibric acid | 104.8 ± 1.0 † | 101.4 ± 3.8 † | D | 227 ± 33 | 36.3 ± 5.8 | - | - |
Griseofulvin | 23.4 ± 1.8 [41] | 29.2 ± 3.4 [41] | S | 3.7 ± 0.6 | 2.4 ± 0.02 | - | - |
Indomethacin | 421.7 ± 17.6 [7] | 109.0 ± 7.0 [15] | D | 31 ± 1.3 | 16 ± 1.0 | - | - |
Mefenamic acid | 36.6 ± 0.6 † | 33.2 ± 0.7 † | S | 13.9 ± 2.0 | 6.2 ± 0.9 | 11.9 ± 1.0 | 7.9 ± 2.1 |
Naproxen | 1584.8 ± 101.4 * | 408.0 ± 35.1 * | D | 144 ± 12 | 38 ± 1.5 | 179 ± 11 | - |
Noscapine | 13.4 ‡ | - | S | 1.1 ± 0.2 | 13.8 ± 1.3 | 1.2 ± 0.1 | 5.2 ± 0.8 |
Progesterone | 25.5 ± 1.1 [50] | 78.6 ± 16.2 [41] | S | 16.8 ± 0.5 | 24.5 ± 5.7 | - | - |
Tadalafil | 5.9 ± 0.7 [7] | 21.0 ± 0.5 † | S | 3.4 ± 0.7 | 7.0 ± 0.9 | 1.3 ± 0.8 | - |
Tolfenamic acid | 63.0 ± 2.7 [15] | 41.0 ± 0.5 [15] | S | 4.1 ± 0.8 | 2.9 ± 0.2 | 12.9 ± 0.9 | 4.8 ± 0.6 |
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Teleki, A.; Nylander, O.; Bergström, C.A.S. Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media. Pharmaceutics 2020, 12, 493. https://doi.org/10.3390/pharmaceutics12060493
Teleki A, Nylander O, Bergström CAS. Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media. Pharmaceutics. 2020; 12(6):493. https://doi.org/10.3390/pharmaceutics12060493
Chicago/Turabian StyleTeleki, Alexandra, Olivia Nylander, and Christel A.S. Bergström. 2020. "Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media" Pharmaceutics 12, no. 6: 493. https://doi.org/10.3390/pharmaceutics12060493
APA StyleTeleki, A., Nylander, O., & Bergström, C. A. S. (2020). Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media. Pharmaceutics, 12(6), 493. https://doi.org/10.3390/pharmaceutics12060493