A nifedipine coground mixture with sodium deoxycholate. I. Colloidal particle formation and solid-state analysis

Sodium deoxycholate (DCNa) is a bile salt that forms multimolecular inclusi on compounds with a variety of organic substances. In this study, complex f ormulation of DCNa with nifedipine, a poorly water soluble drug, by grindin g was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction, differential scanning calorimetry (DSC), and Fourier transform infrared (F TIR) spectroscopy. A laser diffraction particle size analyzer was also used to determine the particle size distribution curve in solution. When a nife dipine-DCNa (1:2 w/w) mixture coground for 30 min was dispersed into water and a pH 6.8 buffer solution, a semitransparent colloidal solution occurred immediately; 90% of the total particles formed in solution had a diameter less than 600 nm. Both powder X-ray diffraction peaks and DSC endothermic p eak of nifedipine crystals were not found for the coground mixture, whereas a new exothermic peak was observed on DSC thermograms. The magnitude of th is exothermic peak depended on the weight fraction of DCNa and the grinding time, indicating that nifedipine crystals changed into an amorphous state by complex formation with DCNa during the grinding process. In the FTIR spe ctrum of the coground mixture, the peaks of aromatic CH out-of-plane bend a nd dihydropyridine NH stretch of nifedipine were considerably weakened, sug gesting that van der Waals interaction may be present between the drug and DCNa molecules. From these results, it is clear that the cogrinding method with DCNa is very useful for the formation of amorphous nifedipine in the s olid state and the production of colloidal particles of the drug in solutio n.