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Pharmaceutics 2014, 6(3), 416-435; doi:10.3390/pharmaceutics6030416

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

Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark
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Received: 28 May 2014 / Revised: 23 June 2014 / Accepted: 1 July 2014 / Published: 14 July 2014
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Abstract

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 the co-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 the co-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 in co-amorphous NAP–ARG. In comparison to crystalline NAP, binary NAP–TRP and NAP–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 of co-amorphous formulations. View Full-Text
Keywords: amino acid; co-amorphous; dissolution rate; DSC; FTIR; salt formation; solid state analysis; stability; XRPD amino acid; co-amorphous; dissolution rate; DSC; FTIR; salt formation; solid state analysis; stability; XRPD
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MDPI and ACS Style

Jensen, K.T.; Löbmann, K.; Rades, T.; Grohganz, H. Improving Co-Amorphous Drug Formulations by the Addition of the Highly Water Soluble Amino Acid, Proline. Pharmaceutics 2014, 6, 416-435.

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