Solid State Chemistry Research Of Nifedipine

The stability of drug plays an important role in its whole life including: research,development,manufacture,and clinical use,even relating to the safety of human life.Nowadays,many marketed drugs still have some stability problems with light,humidity,temperature,heat,or oxygen,etc.Obviously,these factors will make drugs partially decomposed to impurities.Coated tablets,membranes,microcapsule,or inclusion approaches are used to solve the stability problems,but these methods are expensive and complicated,and can't figure out the problems fundamentally.The stability of crystalline drugs is not only affected by the environmental factors but also influenced by the internal molecular arrangement.For most active pharmaceutical ingredients(APIs),there are numerous possible solid forms that can be divided into amorphous,polymorph,solvate,cocrystal,or salt,according to the different arrangement or conformation of API molecules and the type or form of other molecules crystallize with APIs.Each solid form of a defined API may present distinct physicochemical properties,such as solubility,dissolution rate,hygroscopicity,bioavailability,mechanical property and stability.Nifedipine(NFD)belongs to the dihydropyridine antihypertensive drug with the disadvantage of highly photosensitivity.In our research,the remaining content of NFD is only 83% after the illumination of 10 hours.In order to solve this problem,experiments of design and screening polymorphism and cocrystals were performed.Successfully,four solvates(1,4-dioxane form I and II,morpholine form I and II)and five cocrystals(isonicotinamide form I and II,picolinamide,4,4-dipyridine and 4,4-dipyridine methanol solvate)were synthesized and carried out with comprehensive characterization.It was found that form I of cocrystallization with isonicotinamide exhibited higher light stability than form II and other cocrystals.This research may extend the application of cocrystallization to solve other dihydropyridine drugs.