Improving Co-Amorphous Drug Formulations by the Addition of the Highly Water Soluble Amino Acid, Proline

Pharmaceutics

Katrine Tarp Jensen¹  Korbinian Löbmann¹  Thomas Rades¹ 

[1] Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark

关键词: amino acid;    co-amorphous;    dissolution rate;    DSC;    FTIR;    salt formation;    solid state analysis;    stability;    XRPD;   

DOI  :  10.3390/pharmaceutics6030416

来源: mdpi

【 摘 要 】

Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand theco-amorphous drug amino acid mixture approach by combining the model drug, naproxen (NAP), with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG) and a second highly soluble amino acid (proline, PRO) for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared by ball milling and investigated for solid state characteristics, stability and the dissolution rate enhancement of NAP. All co-amorphous mixtures were stable at room temperature and 40 °C for a minimum of 84 days. PRO acted as a stabilizer for theco-amorphous system, including NAP–TRP, through enhancing the molecular interactions in the form of hydrogen bonds between all three components in the mixture. A salt formation between the acidic drug, NAP, and the basic amino acid, ARG, was found inco-amorphous NAP–ARG. In comparison to crystalline NAP, binary NAP–TRP andNAP–ARG, it could be shown that the highly soluble amino acid, PRO, improved the dissolution rate of NAP from the ternary co-amorphous systems in combination with either TRP or ARG. In conclusion, both the solubility of the amino acid and potential interactions between the molecules are critical parameters to consider in the development ofco-amorphous formulations.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.