TY - JOUR

T1 - Dipeptides as co-formers in co-amorphous systems

AU - Wu, Wenqi

AU - Löbmann, Korbinian

AU - Schnitzkewitz, Jan

AU - Knuhtsen, Astrid

AU - Pedersen, Daniel Sejer

AU - Rades, Thomas

AU - Grohganz, Holger

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Drug-amino acid co-amorphous systems have become increasingly well-investigated systems to improve dissolution rate of poorly water-soluble drugs. In this study, dipeptides were investigated as co-formers for co-amorphous systems based on the hypothesis that dipeptides might combine the inherent properties of the two included amino acids. Co-amorphization of the model drug mebendazole was investigated with five dipeptides, tryptophan-phenylalanine, phenylalanine-tryptophan, aspartic acid-tyrosine, histidine-glycine and proline-tryptophan. The dipeptides were chosen to investigate whether the side chains (nonpolar, polar, basic and acidic), and the sequence of amino acids (tryptophan-phenylalanine versus phenylalanine-tryptophan) have an influence on the performance of dipeptides as co-formers. All mebendazole-dipeptide systems became amorphous after ball milling for only 30 min, while this generally was not the case for the single amino acids or physical mixtures of the amino acids forming the dipeptides. Dissolution studies showed that the dissolution rate of mebendazole from most co-amorphous systems was increased significantly compared to crystalline and amorphous mebendazole. However, no clear trend for the drug dissolution enhancement was observed within the different co-amorphous drug-dipeptide systems. The stability study revealed that co-amorphous mebendazole-dipeptide systems showed higher physical stability compared to amorphous mebendazole. In conclusion, dipeptides are shown to be promising co-formers for co-amorphous systems.

AB - Drug-amino acid co-amorphous systems have become increasingly well-investigated systems to improve dissolution rate of poorly water-soluble drugs. In this study, dipeptides were investigated as co-formers for co-amorphous systems based on the hypothesis that dipeptides might combine the inherent properties of the two included amino acids. Co-amorphization of the model drug mebendazole was investigated with five dipeptides, tryptophan-phenylalanine, phenylalanine-tryptophan, aspartic acid-tyrosine, histidine-glycine and proline-tryptophan. The dipeptides were chosen to investigate whether the side chains (nonpolar, polar, basic and acidic), and the sequence of amino acids (tryptophan-phenylalanine versus phenylalanine-tryptophan) have an influence on the performance of dipeptides as co-formers. All mebendazole-dipeptide systems became amorphous after ball milling for only 30 min, while this generally was not the case for the single amino acids or physical mixtures of the amino acids forming the dipeptides. Dissolution studies showed that the dissolution rate of mebendazole from most co-amorphous systems was increased significantly compared to crystalline and amorphous mebendazole. However, no clear trend for the drug dissolution enhancement was observed within the different co-amorphous drug-dipeptide systems. The stability study revealed that co-amorphous mebendazole-dipeptide systems showed higher physical stability compared to amorphous mebendazole. In conclusion, dipeptides are shown to be promising co-formers for co-amorphous systems.

U2 - 10.1016/j.ejpb.2018.11.016

DO - 10.1016/j.ejpb.2018.11.016

M3 - Journal article

C2 - 30468836

AN - SCOPUS:85056907983

VL - 134

SP - 68

EP - 76

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -