Enhancing the Solubility and Dissolution Performance of Safinamide Using Salts
Abstract
:1. Introduction
2. Materials and Methods
2.1. Instrumentations and Materials
2.2. Preparation of Safinamide Salts
2.3. Solubility and Intrinsic Dissolution Rate (IDR) Studies
2.4. Stability Studies
3. Results
3.1. Crystal Structure Analysis
3.1.1. Crystal Structure of SAF-HCl (1:1) Salt
3.1.2. Crystal Structure of SAF-HBr (1:1) Salt
3.1.3. Crystal Structure of SAF/MA (1:1) Salt
3.1.4. Crystal Structure of SAF/MA/H2O (1:1:1) Salt Hydrate
3.2. Powder X-ray Diffraction (PXRD) Analyse
3.3. Thermal Analyses
3.4. Solubility and Dissolution Studies
3.5. Stability Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Title | SAF-HCl | SAF-HBr | SAF-MA | SAF-MA-H2O |
---|---|---|---|---|
Chemical formula | C17H20N2O2F+, Cl− | C17H20N2O2F+, Br− | C17H20N2O2F+, C4H3O4− | C17H20N2O2F+, C4H3O4−, H2O |
Molecular formula | C17H20N2O2FCl | C17H20N2O2FBr | C21H24N2O6F | C21H25N2O7F |
Formula weight | 338.80 | 383.26 | 418.41 | 436.43 |
Crystal system | orthorhombic | orthorhombic | orthorhombic | triclinic |
Space group | P212121 | P212121 | P212121 | P1 |
a [Å] | 5.2766(8) | 5.2340(4) | 5.7326(5) | 5.9202(8) |
b [Å] | 12.174(2) | 13.8352(11) | 9.2498(12) | 8.5781(11) |
c [Å] | 26.389(5) | 24.0985(17) | 38.155(4) | 11.8413(15) |
α[°] | 90 | 90 | 90 | 105.072(11) |
β[°] | 90 | 90 | 90 | 101.299(11) |
γ[°] | 90 | 90 | 90 | 105.145(11) |
Z | 4 | 4 | 4 | 1 |
V (Å3) | 1695.2(5) | 1745.1(2) | 2023.2(4) | 537.57(12) |
Dcalc (g cm−3) | 1.327 | 1.459 | 1.374 | 1.348 |
μ (mm−1) | 0.246 | 2.376 | 0.107 | 0.107 |
R1 (I > 2σ (I)) | 0.0633 | 0.0449 | 0.0809 | 0.0512 |
wR2 (all data, F2) | 0.0780 | 0.0783 | 0.1372 | 0.1062 |
GOF | 0.955 | 0.994 | 1.062 | 1.029 |
Rint | 0.0537 | 0.0588 | 0.0917 | 0.0323 |
Largest diff. peak and hole (e·Å−3) | 0.200/−0.182 | 0.416/−0.331 | 0.184/−0.205 | 0.153/−0.124 |
CCDC | 2010647 | 2010646 | 2010649 | 2010648 |
H-Bond | d(D−H) | d(H···A) | d(D···A) | ∠(DHA) | Symmetry Code |
---|---|---|---|---|---|
SAF-HCl | |||||
N1+−H1A···Cl1 | 0.97 | 2.46 | 3.366(4) | 156 | −x, y−1/2, −z+1/2 |
N1+−H1B···Cl1 | 0.89 | 2.36 | 3.219(4) | 164 | −x, y−1/2, −z+1/2 |
N2−H2A···Cl1 | 0.86 | 2.37 | 3.228(4) | 175 | x, y−1, z |
N2−H2B···Cl1 | 0.89 | 2.56 | 3.332(4) | 145 | x−1, y−1, z |
SAF-HBr | |||||
N1+−H1A···Br1 | 0.89 | 2.54 | 3.436(4) | 176 | −x+1, y+1/2, −z+1/2 |
N1+−H1B···Br1 | 1.04 | 2.45 | 3.410(4) | 152 | −x+1, y+1/2, −z+1/2 |
N2−H2A···Br1 | 0.86 | 2.79 | 3.503(4) | 141 | x+1, y+1, z |
N2−H2B···Br1 | 0.86 | 2.59 | 3.443(4) | 170 | x, y+1, z |
SAF-MA | |||||
N1+−H1A···O3 | 0.87 | 1.89 | 2.760(5) | 174 | x, y, z |
N1+−H1B···O4 | 1.01 | 2.05 | 3.049(5) | 169 | x−1, y, z |
N2−H2A···O2 | 0.96 | 1.97 | 2.908(5) | 163 | −x+1, y−1/2, −z+1/2 |
N2−H2B···O5 | 0.90 | 2.35 | 3.066(5) | 137 | −x+1, y−1/2, −z+1/2 |
O5−H5···O4 | 0.94 | 1.51 | 2.439(5) | 173 | x, y, z |
SAF-MA-H2O | |||||
N1+−H1A···O7 | 0.90 | 1.92 | 2.787(3) | 161 | x, y−1, z |
N1+−H1B···O6 | 0.90 | 1.99 | 2.825(3) | 153 | x, y, z |
N2−H2A···O3 | 0.86 | 2.07 | 2.909(3) | 166 | x+1, y, z+1 |
N2−H2B···O4 | 0.87 | 2.19 | 3.000(3) | 155 | x, y, z+1 |
O7−H7C···O6 | 0.90 | 2.09 | 2.846(3) | 141 | x−1, y+1, z |
O4−H4···O5 | 0.90 | 1.62 | 2.402(3) | 142 | x, y, z |
Compound | Aqueous Solubility (mg/mL) | Solubility at pH 6.86 (mg/mL) | IDR in Aqueous Medium (mg/cm2/min) | IDR at pH 6.86 (mg/cm2/min) |
---|---|---|---|---|
SAF | 0.19 | 0.39 | 0.013 | 0.024 |
SAF-HCl | 30.86 | 26.59 | 4.16 | 0.14 |
SAF-HBr | 24.93 | 16.69 | 6.03 | 1.49 |
SAF-MA | Unstable | Unstable | 0.67 | 0.037 |
SAF-MA-H2O | 6.66 | 5.18 | 0.64 | 0.035 |
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Gao, L.; Liu, Q.; Zhang, X.-R. Enhancing the Solubility and Dissolution Performance of Safinamide Using Salts. Crystals 2020, 10, 989. https://doi.org/10.3390/cryst10110989
Gao L, Liu Q, Zhang X-R. Enhancing the Solubility and Dissolution Performance of Safinamide Using Salts. Crystals. 2020; 10(11):989. https://doi.org/10.3390/cryst10110989
Chicago/Turabian StyleGao, Lei, Qian Liu, and Xian-Rui Zhang. 2020. "Enhancing the Solubility and Dissolution Performance of Safinamide Using Salts" Crystals 10, no. 11: 989. https://doi.org/10.3390/cryst10110989