The Crystal Structure Design And Bioavailability Research Of Candesartan

Polymorphic drugs are refered to the active pharmaceutical ingredient(API) of the solid drugs exiting in a specific crystalline state. Because a solid drug’ s thermal and chemical stability, in vivo dissolution and bioavailability can be affected by its dirrerent crystal forms more and more attentation has been attracted to polymorphic drugs. While exploring new crystal forms that can effectively improve a drug’ s physical and chemical properties has become a research hotspot of polymorphic drugs.In this research, an anti-hypertensive drug Candesartan worked as the active pharmaceutical ingredients, ethylenediamine, 1, 3-diaminopropane and ammonia as alkaline reagents, sceened new crystal forms by solvent assisted grinding method and successfully synthesized three novel crystals of candesartan with ethylenediamine[H3N(CH2)2NH3)][can]·2H2O(1), 1, 3-diaminopropane [H3N(CH2)3NH3][can]·2H2O(2)and ammonia [NH4][Hcan](3)(Candesartan shorthand for H2can) using solvent evaporation method and then were characterized by single and powder X-ray diffraction,DSC, TGA, 1HNMR and IR spectroscopy. According to in vitro solubility studies, the three candesartan salts exhibited significantly higher aqueous solubilities. The bioavailability of these fast dissolving salts also showed dramacticlly enhancement by 1.3, 2.57 and 3.14 times respectively than candesartan.Study on polymorphic drugs is the guarantee of development level and drug quaility safety of modern chemical drugs.Three novel crystal forms prepared in this research with obviously increased bioavailability have provided powerful technical support for the medicament development of candesartan.