Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems

Research output: Contribution to journalJournal articlepeer-review

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Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems. / Liu, Jingwen; Rades, Thomas; Grohganz, Holger.

In: Molecular Pharmaceutics, Vol. 17, No. 4, 2020, p. 1335-1342.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Liu, J, Rades, T & Grohganz, H 2020, 'Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems', Molecular Pharmaceutics, vol. 17, no. 4, pp. 1335-1342. https://doi.org/10.1021/acs.molpharmaceut.0c00042

APA

Liu, J., Rades, T., & Grohganz, H. (2020). Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems. Molecular Pharmaceutics, 17(4), 1335-1342. https://doi.org/10.1021/acs.molpharmaceut.0c00042

Vancouver

Liu J, Rades T, Grohganz H. Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems. Molecular Pharmaceutics. 2020;17(4):1335-1342. https://doi.org/10.1021/acs.molpharmaceut.0c00042

Author

Liu, Jingwen ; Rades, Thomas ; Grohganz, Holger. / Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems. In: Molecular Pharmaceutics. 2020 ; Vol. 17, No. 4. pp. 1335-1342.

Bibtex

@article{95d97079a30b4603894c7ca765f0a256,
title = "Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems",
abstract = "Coamorphous drug formulations are a promising approach to improve solubility and bioavailability of poorly water-soluble drugs. On the basis of theoretical assumptions involving molecular interactions, the 1:1 molar ratio of drug and coformer is frequently used as {"}the optimal ratio{"} for a homogeneous coamorphous system (i.e., the coamorphous system with the highest physical stability and, if strong interaction is possible between two molecules, the highest glass transition temperature (T-g)). In order to more closely investigate this assumption, L-aspartic acid (ASP) and L-glutamic acid (GLU) were investigated as coformers for the basic drug carvedilol (CAR) at varying molar ratios. Salt formation between CAR with ASP or GLU was expected to occur at the molar 1:1 ratio based on their chemical structures. Interestingly, the largest deviation between the experimental T-g and the theoretical T-g based on the Gordon-Taylor equation was observed at a molar ratio of around 1:1.5 in CAR-ASP and CAR-GLU systems. In order to determine the exact value of the ratio with the highest T-g, a data fitting approach was established on thermometric data of various CAR-ASP and CAR-GLU systems. The highest T-g was found to be at CAR- ASP 1:1.46 and CAR-GLU 1:1.43 mathematically. Spectroscopic investigations and physical stability measurements further confirmed that the optimal molar ratio for obtaining a homogeneous system and the highest stability can be found at a molar ratio around 1:1.5. Overall, this study developed a novel approach to determine the optimal ratio between drug and coformers and revealed the influence of varying molar ratios on molecular interactions and physical stability in coamorphous systems.",
keywords = "coamorphous, amino acids, molar ratio, molecular interactions, physical stability, WATER-SOLUBLE DRUGS, CO-AMORPHOUS STABILIZERS, SOLID DISPERSION, DISSOLUTION, INDOMETHACIN, SOLUBILITY",
author = "Jingwen Liu and Thomas Rades and Holger Grohganz",
year = "2020",
doi = "10.1021/acs.molpharmaceut.0c00042",
language = "English",
volume = "17",
pages = "1335--1342",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "4",

}

RIS

TY - JOUR

T1 - Determination of the Optimal Molar Ratio in Amino Acid-Based Coamorphous Systems

AU - Liu, Jingwen

AU - Rades, Thomas

AU - Grohganz, Holger

PY - 2020

Y1 - 2020

N2 - Coamorphous drug formulations are a promising approach to improve solubility and bioavailability of poorly water-soluble drugs. On the basis of theoretical assumptions involving molecular interactions, the 1:1 molar ratio of drug and coformer is frequently used as "the optimal ratio" for a homogeneous coamorphous system (i.e., the coamorphous system with the highest physical stability and, if strong interaction is possible between two molecules, the highest glass transition temperature (T-g)). In order to more closely investigate this assumption, L-aspartic acid (ASP) and L-glutamic acid (GLU) were investigated as coformers for the basic drug carvedilol (CAR) at varying molar ratios. Salt formation between CAR with ASP or GLU was expected to occur at the molar 1:1 ratio based on their chemical structures. Interestingly, the largest deviation between the experimental T-g and the theoretical T-g based on the Gordon-Taylor equation was observed at a molar ratio of around 1:1.5 in CAR-ASP and CAR-GLU systems. In order to determine the exact value of the ratio with the highest T-g, a data fitting approach was established on thermometric data of various CAR-ASP and CAR-GLU systems. The highest T-g was found to be at CAR- ASP 1:1.46 and CAR-GLU 1:1.43 mathematically. Spectroscopic investigations and physical stability measurements further confirmed that the optimal molar ratio for obtaining a homogeneous system and the highest stability can be found at a molar ratio around 1:1.5. Overall, this study developed a novel approach to determine the optimal ratio between drug and coformers and revealed the influence of varying molar ratios on molecular interactions and physical stability in coamorphous systems.

AB - Coamorphous drug formulations are a promising approach to improve solubility and bioavailability of poorly water-soluble drugs. On the basis of theoretical assumptions involving molecular interactions, the 1:1 molar ratio of drug and coformer is frequently used as "the optimal ratio" for a homogeneous coamorphous system (i.e., the coamorphous system with the highest physical stability and, if strong interaction is possible between two molecules, the highest glass transition temperature (T-g)). In order to more closely investigate this assumption, L-aspartic acid (ASP) and L-glutamic acid (GLU) were investigated as coformers for the basic drug carvedilol (CAR) at varying molar ratios. Salt formation between CAR with ASP or GLU was expected to occur at the molar 1:1 ratio based on their chemical structures. Interestingly, the largest deviation between the experimental T-g and the theoretical T-g based on the Gordon-Taylor equation was observed at a molar ratio of around 1:1.5 in CAR-ASP and CAR-GLU systems. In order to determine the exact value of the ratio with the highest T-g, a data fitting approach was established on thermometric data of various CAR-ASP and CAR-GLU systems. The highest T-g was found to be at CAR- ASP 1:1.46 and CAR-GLU 1:1.43 mathematically. Spectroscopic investigations and physical stability measurements further confirmed that the optimal molar ratio for obtaining a homogeneous system and the highest stability can be found at a molar ratio around 1:1.5. Overall, this study developed a novel approach to determine the optimal ratio between drug and coformers and revealed the influence of varying molar ratios on molecular interactions and physical stability in coamorphous systems.

KW - coamorphous

KW - amino acids

KW - molar ratio

KW - molecular interactions

KW - physical stability

KW - WATER-SOLUBLE DRUGS

KW - CO-AMORPHOUS STABILIZERS

KW - SOLID DISPERSION

KW - DISSOLUTION

KW - INDOMETHACIN

KW - SOLUBILITY

U2 - 10.1021/acs.molpharmaceut.0c00042

DO - 10.1021/acs.molpharmaceut.0c00042

M3 - Journal article

C2 - 32119557

VL - 17

SP - 1335

EP - 1342

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 4

ER -

ID: 245619907