methylcellulose and 1-4-dihydropyridine

Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed. In this study, employing microwave technology as a new means to improve solubility, we established a method for preparing solid dispersions using hydroxypropyl methylcellulose acetate succinate as a polymeric carrier and urea as a third component. This effective method has a treatment time of several minutes (simple) and does not require the use of organic solvents (low environmental impact). The third component, urea, acts to lower the melting point of NZ-105, which promotes amorphization. This greatly improves the solubility compared with the microwave-treated product of NZ-105/HPMC-AS binary system. The solid dispersion prepared with this method, in addition to evaluation in vitro, was tested in vivo using beagle dogs and shown to be effective from the eightfold improvement in absorption compared with NZ-105 alone based on the area under the curve.

Topics: Animals; Area Under Curve; Calorimetry, Differential Scanning; Dihydropyridines; Dogs; Drug Carriers; Hot Temperature; Magnetic Resonance Spectroscopy; Male; Methylcellulose; Microwaves; Nitrophenols; Organic Chemicals; Organophosphorus Compounds; Solubility; Solvents; Urea; X-Ray Diffraction