A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan
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A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan. / Di, Rong; Liu, Jingwen; Grohganz, Holger; Rades, Thomas.
In: Molecules, Vol. 26, No. 4, 801, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A Multivariate Approach for the Determination of the Optimal Mixing Ratio of the Non-Strong Interacting Co-Amorphous System Carvedilol-Tryptophan
AU - Di, Rong
AU - Liu, Jingwen
AU - Grohganz, Holger
AU - Rades, Thomas
PY - 2021
Y1 - 2021
N2 - Converting crystalline compounds into co-amorphous systems is an effective way to improve the solubility of poorly water-soluble drugs. It is, however, of critical importance for the physical stability of co-amorphous systems to find the optimal mixing ratio of the drug with the co-former. In this study, a novel approach for this challenge is presented, exemplified with the co-amorphous system carvedilol-tryptophan (CAR-TRP). Following X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) of the ball-milled samples to confirm their amorphous form, Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were applied to investigate intermolecular interactions. A clear deviation from a purely additive spectrum of CAR and TRP was visualized in the PCA score plot, with a maximum at around 30% drug (mol/mol). This deviation was attributed to hydrogen bonds of CAR with TRP ether groups. The sample containing 30% drug (mol/mol) was also the most stable sample during a stability test. Using the combination of FTIR with PCA is an effective approach to investigate the optimal mixing ratio of non-strong interacting co-amorphous systems.
AB - Converting crystalline compounds into co-amorphous systems is an effective way to improve the solubility of poorly water-soluble drugs. It is, however, of critical importance for the physical stability of co-amorphous systems to find the optimal mixing ratio of the drug with the co-former. In this study, a novel approach for this challenge is presented, exemplified with the co-amorphous system carvedilol-tryptophan (CAR-TRP). Following X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) of the ball-milled samples to confirm their amorphous form, Fourier-transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were applied to investigate intermolecular interactions. A clear deviation from a purely additive spectrum of CAR and TRP was visualized in the PCA score plot, with a maximum at around 30% drug (mol/mol). This deviation was attributed to hydrogen bonds of CAR with TRP ether groups. The sample containing 30% drug (mol/mol) was also the most stable sample during a stability test. Using the combination of FTIR with PCA is an effective approach to investigate the optimal mixing ratio of non-strong interacting co-amorphous systems.
KW - co-amorphous systems
KW - optimal mixing ratio
KW - glass transition temperature
KW - principal component analysis
U2 - 10.3390/molecules26040801
DO - 10.3390/molecules26040801
M3 - Journal article
C2 - 33557164
VL - 26
JO - Molecules (Print Archive Edition)
JF - Molecules (Print Archive Edition)
SN - 1431-5157
IS - 4
M1 - 801
ER -
ID: 261216115