Co-former selection for co-amorphous drug-amino acid formulations

Publication date: Available online 19 December 2018Source: International Journal of PharmaceuticsAuthor(s): Georgia Kasten, Korbinian Löbmann, Holger Grohganz, Thomas RadesAbstractWe have previously developed a fast screening method on the ability of twenty amino acids (AA) to form co-amorphous formulations with six drugs upon ball milling. In this work, the potential advantages in physical stability and dissolution rate of the 36 successful co-amorphous formulations, compared to the pure amorphous drug, were further investigated. The physical stability of the formulations at dry conditions was assessed by X-ray powder diffraction (XRPD) and their thermal behavior by differential scanning calorimetry (DSC). In addition, the intrinsic dissolution rate (IDR) of all formulations was determined in phosphate buffer (10 mM, pH 6.8). Finally, all the co-amorphous formulations were summarized into different groups, according to the outcome of the co-formability, physical stability and dissolution rate screenings, and guidelines could be drawn for selection of co-formers for a new given drug: (i) For acidic drugs, basic AAs (arginine, histidine, and lysine) are good co-formers with respect to the three critical quality attributes: co-formability, physical stability and dissolution. High glass transition temperatures (Tg), physical stability for 1-2 years, and accelerated IDR were observed. (ii) For basic and neutral drugs, non-polar AAs with aromatic groups such as tryptophan (TRP) a...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research