Purpose: To change the dissolution properties of indomethacin, a non-steroidal anti-inflammatory drug characterized by weak solubility and bioavailability, we propose the preparation of co-crystals where the active pharmaceutical ingredient is indomethacin and the partners are aromatic nitrogen bases (+ 2-hydroxy-4-methyl-pyridine or 2-methoxy-5-nitro-anyline) or saccharine. In co-crystals different molecules are linked in the same crystalline lattice by intermolecular interactions, so can be defined supramolecular complexes. Methods: The packing of structures have been determined with the employment of a X-ray Nonius Kappa CCD diffractometer and have been analyzed from the point of view of intermolecular interactions. The dissolution studies have been performed by incubation of free or co-crystalized indomethacin in phosphate buffer whose concentrations have been analyzed by HPLC during time. Results: The carboxylic group usually forms COOH...HOOC homosyntons to give dimers, using other functional groups to interact via H bond with the partners. In all co-crystals indomethacin has showed significantly different solubility and dissolution rates with respect to those of the free drug. The simple mix of indomethacin and partners without co-crystallization processes showed for indomethacin the same solubility and dissolution rate of the pure drug. Conclusions: The co-crystallization with appropriate partners can induce important changes in solubility and dissolution rates of indomethacin allowing to hypothesize interesting influences in the bioavailability or local delivery of the drug.
Preparation, characterization and dissolution studies of pharmaceutical co-crystals containing indomethacin
DALPIAZ, Alessandro;BERTOLASI, Valerio;FERRETTI, Valeria
2013
Abstract
Purpose: To change the dissolution properties of indomethacin, a non-steroidal anti-inflammatory drug characterized by weak solubility and bioavailability, we propose the preparation of co-crystals where the active pharmaceutical ingredient is indomethacin and the partners are aromatic nitrogen bases (+ 2-hydroxy-4-methyl-pyridine or 2-methoxy-5-nitro-anyline) or saccharine. In co-crystals different molecules are linked in the same crystalline lattice by intermolecular interactions, so can be defined supramolecular complexes. Methods: The packing of structures have been determined with the employment of a X-ray Nonius Kappa CCD diffractometer and have been analyzed from the point of view of intermolecular interactions. The dissolution studies have been performed by incubation of free or co-crystalized indomethacin in phosphate buffer whose concentrations have been analyzed by HPLC during time. Results: The carboxylic group usually forms COOH...HOOC homosyntons to give dimers, using other functional groups to interact via H bond with the partners. In all co-crystals indomethacin has showed significantly different solubility and dissolution rates with respect to those of the free drug. The simple mix of indomethacin and partners without co-crystallization processes showed for indomethacin the same solubility and dissolution rate of the pure drug. Conclusions: The co-crystallization with appropriate partners can induce important changes in solubility and dissolution rates of indomethacin allowing to hypothesize interesting influences in the bioavailability or local delivery of the drug.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.