Isavuconazole: Thermodynamic Evaluation of Processes Sublimation, Dissolution and Partition in Pharmaceutically Relevant Media
Abstract
:1. Introduction
2. Results and Discussion
2.1. Thermophysical Properties
2.2. Sublimation
2.2.1. Experimental Results
2.2.2. Clusterization Approach
2.3. Solubility
2.4. Hansen Solubility Parameters
2.5. Solubility Data Modeling
2.6. Dissolution Thermodynamics
2.7. Lipophilicity
3. Materials and Methods
3.1. Materials
3.2. Differential Scanning Calorimetry
3.3. Powder X-ray Diffraction
3.4. Vapor Pressure Measurements
3.5. Solubility
3.6. Partition Experiment
3.7. Theoretical Basis
3.7.1. Hansen Solubility Parameters
3.7.2. Modified Apelblat Model
3.7.3. Van’t Hoff Equation
3.7.4. Data Correlation
3.8. Dissolution Thermodynamics
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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aT/K | b 103 m/mg | cV(N2)/dm3 | dTa/K | Flow/dm3·h−1 | 103 p/Pa | lnp |
---|---|---|---|---|---|---|
365.15 | 3.38 | 9.802 | 297.15 | 1.69 | 1.95 | −6.241 |
367.15 | 4.09 | 9.210 | 296.15 | 1.69 | 2.50 | −5.991 |
369.15 | 5.16 | 9.092 | 295.15 | 1.69 | 3.19 | −5.749 |
371.15 | 6.76 | 9.430 | 295.15 | 1.69 | 4.02 | −5.515 |
372.15 | 7.74 | 9.548 | 295.15 | 1.69 | 4.55 | −5.393 |
373.15 | 8.72 | 9.582 | 295.15 | 1.69 | 5.11 | −5.277 |
374.15 | 9.35 | 9.160 | 295.15 | 1.69 | 5.72 | −5.163 |
376.15 | 11.48 | 8.923 | 295.15 | 1.69 | 7.22 | −4.931 |
378.15 | 14.69 | 9.329 | 295.15 | 1.69 | 8.83 | −4.729 |
379.15 | 15.84 | 9.041 | 295.15 | 1.69 | 9.83 | −4.622 |
380.15 | 17.09 | 8.568 | 295.15 | 1.69 | 11.19 | −4.493 |
381.15 | 20.21 | 9.244 | 296.15 | 1.69 | 12.30 | −4.398 |
382.15 | 20.92 | 8.534 | 296.15 | 1.69 | 13.79 | −4.283 |
383.15 | 23.59 | 8.636 | 296.15 | 1.60 | 15.37 | −4.175 |
/kJ·mol−1 | 68.9 ± 0.2 | |||||
/kJ·mol−1 | 138.1 ± 0.5 | |||||
/J·mol−1·K−1 | −71.8 | |||||
/J·mol−1·K−1 | 230.4 ± 4.6 |
T/K | a Buffer pH 1.2 | b Buffer pH 2.0 | c Buffer pH 7.4 | Hexane | Ethanol | 1-Propanol | 1-Octanol |
---|---|---|---|---|---|---|---|
(S·105) | (S·105) | (S·106) | (S·104) | (S·101) | (S·101) | (S·102) | |
293.15 | 3.80 | 1.03 | 6.67 | 4.23 | 1.47 | 1.01 | 3.89 |
298.15 | 4.24 | 1.23 | 8.13 | 5.37 | 1.77 | 1.20 | 4.67 |
303.15 | 4.74 | 1.49 | 10.00 | 6.77 | 2.11 | 1.43 | 5.50 |
308.15 | 5.25 | 1.79 | 12.16 | 8.47 | 2.50 | 1.68 | 6.52 |
313.15 | 5.84 | 2.14 | 14.55 | 10.50 | 2.94 | 1.96 | 7.60 |
Compound | V, cm3·mol−1 | δd, MPa0.5 | δp, MPa0.5 | δh, MPa0.5 | δt, MPa0.5 | e Δδt | f ∆δ | δv, MPa0.5 |
---|---|---|---|---|---|---|---|---|
IVZ | 389.7 | 21.8 | 4.3 | 7.3 | 23.4 | - | - | 22.2 |
Buffer solutions | 18.0 | 15.5 | 16.0 | 42.3 | 47.8 | 24.4 | 37.4 | 22.3 |
Hexane | 131.6 | 14.9 | 0.0 | 0.0 | 14.9 | 8.5 | 10.9 | 14.9 |
Ethanol | 58.5 | 15.8 | 8.8 | 19.4 | 26.5 | 3.1 | 14.2 | 18.1 |
1-Propanol | 75.2 | 16.0 | 6.8 | 17.4 | 24.6 | 1.2 | 11.9 | 17.4 |
1-Octanol | 157.7 | 17.0 | 5.0 | 11.9 | 20.6 | 2.8 | 6.7 | 17.7 |
T/K | xexp | Modified Apelblat Equation | van’t Hoff Equation | ||
---|---|---|---|---|---|
xcal | 103·RD | xcal | 103 RD | ||
Buffer pH 1.2 a | |||||
293.15 | 6.8309·10−7 | 6.8301·10−7 | 0.1228 | 6.8234·10−7 | 1.1027 |
298.15 | 7.6422·10−7 | 7.6469·10−7 | −0.6118 | 7.6519·10−7 | −1.2718 |
303.15 | 8.5596·10−7 | 8.5388·10−7 | 2.4392 | 8.5488·10−7 | 1.2713 |
308.15 | 9.4893·10−7 | 9.5109·10−7 | −2.2742 | 9.5164·10−7 | −2.8588 |
313.15 | 10.578·10−7 | 10.568·10−7 | 0.9561 | 10.557·10−7 | 1.9519 |
Buffer pH 2.0 b | |||||
293.15 | 1.8538·10−7 | 1.8489·10−7 | 2.6902 | 1.8386·10−7 | 8.2257 |
298.15 | 2.2156·10−7 | 2.2301·10−7 | −6.5181 | 2.2353·10−7 | −8.8859 |
303.15 | 2.686·10−7 | 2.6872·10−7 | −0.4723 | 2.7002·10−7 | −5.2979 |
308.15 | 3.2558·10−7 | 3.2354·10−7 | 6.2519 | 3.2418·10−7 | 4.2902 |
313.15 | 3.8771·10−7 | 3.8914·10−7 | −3.691 | 3.8694·10−7 | 1.979 |
Buffer pH 7.4 c | |||||
293.15 | 1.1952·10−7 | 1.1915·10−7 | 3.1335 | 1.1936·10−7 | 1.3961 |
298.15 | 1.4591·10−7 | 1.4708·10−7 | −8.0535 | 1.4693·10−7 | −7.0446 |
303.15 | 1.8073·10−7 | 1.7998·10−7 | 4.1779 | 1.7964·10−7 | 6.0225 |
308.15 | 2.1892·10−7 | 2.1840·10−7 | 2.3701 | 2.1821·10−7 | 3.2370 |
313.15 | 2.6240·10−7 | 2.6294·10−7 | −2.0585 | 2.6341·10−7 | −3.8416 |
Hexane | |||||
293.15 | 5.5224·10−5 | 5.5187·10−5 | 0.6774 | 5.5171·10−5 | 0.9647 |
298.15 | 7.0509·10−5 | 7.0549·10−5 | −0.5658 | 7.0584·10−5 | −1.0607 |
303.15 | 8.9532·10−5 | 8.9506·10−5 | 0.2907 | 8.9572·10−5 | −0.4460 |
308.15 | 11.287·10−5 | 11.274·10−5 | 1.1049 | 11.279·10−5 | 0.6517 |
313.15 | 14.101·10−5 | 14.103·10−5 | −0.1695 | 14.099·10−5 | 0.1353 |
Ethanol | |||||
293.15 | 0.9236·10−2 | 0.9240·10−2 | 0.0023 | 0.9213·10−2 | 2.9608 |
298.15 | 1.1339·10−2 | 1.1326·10−2 | 1.2112 | 1.1348·10−2 | −0.7125 |
303.15 | 1.3831·10−2 | 1.3835·10−2 | −0.3595 | 1.3883·10−2 | −3.8107 |
308.15 | 1.6854·10−2 | 1.6844·10−2 | 0.3442 | 1.6873·10−2 | −1.3468 |
313.15 | 2.0450·10−2 | 2.0441·10−2 | 0.4360 | 2.0379·10−2 | 3.4562 |
1-Propanol | |||||
293.15 | 7.9034·10−3 | 7.8833·10−3 | 2.1086 | 7.8924·10−3 | 0.9592 |
298.15 | 9.5491·10−3 | 9.5597·10−3 | −6.2862 | 9.5750·10−3 | −2.6146 |
303.15 | 11.557·10−3 | 11.528·10−3 | 6.2322 | 11.542·10−3 | 1.5228 |
308.15 | 13.829·10−3 | 13.827·10−3 | −1.9602 | 13.830·10−3 | 0.0031 |
313.15 | 16.474·10−3 | 16.501·10−3 | −0.0372 | 16.475·10−3 | −0.3328 |
1-Octanol | |||||
293.15 | 6.2145·10−3 | 6.2160·10−3 | −0.9679 | 6.2245·10−3 | −2.3294 |
298.15 | 7.5228·10−3 | 7.4880·10−3 | 4.2499 | 7.4831·10−3 | 4.9131 |
303.15 | 8.9147·10−3 | 8.9532·10−3 | −4.8528 | 8.9416·10−3 | −3.5518 |
308.15 | 10.657·10−3 | 10.629·10−3 | 2.9069 | 10.623·10−3 | 3.4729 |
313.15 | 12.526·10−3 | 12.534·10−3 | −0.3032 | 12.551·10−3 | −1.6928 |
Solvents | A | B | C | RMSD | 103 RAD |
---|---|---|---|---|---|
Modified Apelblat equation | |||||
Buffer pH 1.2 | −34.28 | −788.9 | 4.01 | 1.43·10−9 | 1.3 |
Buffer pH 2.0 | −133.86 | 2450.3 | 19.36 | 1.31·10−9 | 3.9 |
Buffer pH 7.4 | 41.51 | −5666.2 | −6.71 | 7.28·10−10 | 3.8 |
Hexane | −7.99 | −3725.7 | 1.92 | 5.29·10−9 | 0.6 |
Ethanol | −72.53 | −22.3 | 11.96 | 8.08·10−6 | 0.5 |
1-Propanol | −12.03 | 2544.3 | 2.79 | 4.43·10−5 | 3.3 |
1-Octanol | 39.18 | −4720.7 | −4.96 | 2.84·10−5 | 3.6 |
van’t Hoff equation | |||||
Buffer pH 1.2 | −7.36 | −2003.4 | 1.69·10−9 | 1.7 | |
Buffer pH 2.0 | −3.86 | −3415.4 | 1.47·10−9 | 5.7 | |
Buffer pH 7.4 | −3.55 | −3633.4 | 8.70·10−10 | 4.3 | |
Hexane | 4.88 | −4306.6 | 5.62·10−8 | 0.7 | |
Ethanol | 7.74 | −3644.2 | 4.27·10−5 | 2.5 | |
1-Propanol | 6.68 | −3378.1 | 4.49·10−5 | 4.1 | |
1-Octanol | 5.90 | −3219.1 | 2.97·10−5 | 3.7 |
T/K | lnxid | lnγ∞ | ||||||
---|---|---|---|---|---|---|---|---|
Buffer pH 1.2 | Buffer pH 2.0 | Buffer pH 7.4 | Hexane | Ethanol | 1-Propanol | 1-Octanol | ||
293.15 | −2.68 | 11.51 | 12.82 | 13.26 | 7.12 | 2.00 | 2.16 | 2.40 |
298.15 | −2.53 | 11.55 | 12.80 | 13.21 | 7.03 | 1.95 | 2.12 | 2.36 |
303.15 | −2.37 | 11.59 | 12.76 | 13.15 | 6.95 | 1.91 | 2.09 | 2.34 |
308.15 | −2.22 | 11.64 | 12.72 | 13.11 | 6.86 | 1.86 | 2.06 | 2.32 |
313.15 | −2.08 | 11.67 | 12.69 | 13.08 | 6.79 | 1.81 | 2.03 | 2.30 |
a A | 14.15 ± 0.05 | 10.69 ± 0.1 | 10.34 ± 0.1 | 1.91 ± 0.04 | −0.96 ± 0.02 | 0.11 ± 0.06 | 0.91 ± 0.11 | |
a B | −774 ± 15 | 625 ± 31 | 854 ± 18 | 1526 ± 13 | 867 ± 5 | 598 ± 16 | 435 ± 33 | |
b R | 0.9994 | 0.9962 | 0.9962 | 0.9999 | 0.9999 | 0.9988 | 0.9913 |
Solvent | GE, kJ·mol−1 | HE, kJ·mol−1 | TSE, kJ·mol−1 | SE, J·mol−1·K−1 | a ςHE, % | b ςTSE,% |
---|---|---|---|---|---|---|
Buffer pH 1.2 | 28.6 ± 0.5 | −6.43 ± 0.1 | −35.03 | −117.5 ± 4.1 | 15.3 | 84.7 |
Buffer pH 2.0 | 31.7 ± 0.6 | 5.20 ± 0.3 | −26.50 | −88.9 ± 5.1 | 16.4 | 83.6 |
Buffer pH 7.4 | 32.7 ± 0.6 | 7.10 ± 0.1 | −25.6 | −85.9 ±2.9 | 21.7 | 78.3 |
Hexane | 17.4 ± 0.3 | 12.69 ± 0.1 | −4.71 | −15.8 ± 0.4 | 72.9 | 27.1 |
Ethanol | 4.83 ± 0.1 | 7.21 ± 0.1 | 2.38 | 8.0 ± 0.3 | 75.2 | 24.8 |
1-Propanol | 5.25 ± 0.2 | 4.97 ± 0.1 | −0.28 | −0.9 ± 0.04 | 94.7 | 5.3 |
1-Octanol | 5.85 ± 0.2 | 3.62 ± 0.1 | −2.23 | −7.5 ± 0.3 | 61.9 | 38.1 |
T/K | sO · 103 | sB · 106 | PO/B | logPO/B | xo · 104 | xB · 107 | logP*O/B |
---|---|---|---|---|---|---|---|
293.15 | 2.15 | 6.85 | 313.71 | 2.50 | 3.39 | 1.22 | 3.44 |
298.15 | 2.15 | 5.98 | 359.18 | 2.56 | 3.40 | 1.07 | 3.50 |
303.15 | 2.15 | 5.20 | 413.63 | 2.62 | 3.42 | 0.93 | 3.56 |
308.15 | 2.15 | 4.53 | 474.77 | 2.68 | 3.43 | 0.81 | 3.62 |
313.15 | 2.15 | 4.02 | 535.22 | 2.73 | 3.45 | 0.72 | 3.68 |
Aa | 16.52 ± 0.09 | = −19.99 ± 0.4/kJ·mol−1 | |||||
Ba | 2520 ± 26 | = 20.95 ± 0.2/kJ·mol−1 | |||||
Rb | 0.9998 | = 40.9 ± 1.5/kJ·mol−1 | |||||
σc | 0.8·10−2 | = 137.3 ± 5.2/J·mol−1K−1 |
Chemical Name | CAS Register No. | Formula | M/g mol−1 | Source | Initial Mass Fraction Purity | Final Mass Fraction Purity |
---|---|---|---|---|---|---|
Isavuconazole | 241479-67-4 | C22 H17 F2 N5 O S | 437.5 | Shanghai Send Pharmaceutical Technology | ≥0.99 a | No purification |
Ethanol | 64-17-5 | C2H6O | 46.1 | Sigma-Aldrich | ≥0.99 b | No purification |
1-Propanol | 71-23-8 | C3 H8 O | 60.1 | Sigma-Aldrich | ≥0.99 b | No purification |
1-Octanol | 111-87-5 | C8H18O | 130.2 | Sigma-Aldrich | ≥0.99 b | No purification |
Hexane | 110-54-3 | C6H14 | 86.2 | Sigma-Aldrich | ≥0.97 b | ≥0.98 c |
Potassium dihydrogen phosphate | 7778-77-0 | KH2PO4 | 136.1 | Merck | ≥0.99 c | No purification |
Disodium hydrogen phosphate dodecahydrate | 10039-32-4 | Na2HPO4·12H2O | 358.1 | Merck | ≥0.99 b | No purification |
Potassium chloride | 7447-40-7 | KCl | 74.5 | Sigma-Aldrich | ≥0.99 b | No purification |
Hydrochloric acid mol/dm3 fixanal | 7647-01-0 | Aldrich | - | None | No purification |
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Ol’khovich, M.; Sharapova, A.; Blokhina, S.; Perlovich, G. Isavuconazole: Thermodynamic Evaluation of Processes Sublimation, Dissolution and Partition in Pharmaceutically Relevant Media. Molecules 2021, 26, 4759. https://doi.org/10.3390/molecules26164759
Ol’khovich M, Sharapova A, Blokhina S, Perlovich G. Isavuconazole: Thermodynamic Evaluation of Processes Sublimation, Dissolution and Partition in Pharmaceutically Relevant Media. Molecules. 2021; 26(16):4759. https://doi.org/10.3390/molecules26164759
Chicago/Turabian StyleOl’khovich, Marina, Angelica Sharapova, Svetlana Blokhina, and German Perlovich. 2021. "Isavuconazole: Thermodynamic Evaluation of Processes Sublimation, Dissolution and Partition in Pharmaceutically Relevant Media" Molecules 26, no. 16: 4759. https://doi.org/10.3390/molecules26164759