小分子无定形药物的凝胶化研究

与药物晶态相比,无定形态呈长程无序的分子排列,常表现出较高的表观溶解度和溶出度.然而,一些小分子无定形药物在溶出期间会出现聚集成团的凝胶化现象,并表现出显著低于晶体药物的异常溶出行为.本研究旨在考察无定形药物凝胶化与其异常溶出之间的联系,探索凝胶形成的内在机制.通过熔融冷却法制备了辛伐他汀(simvastatin,SI...

Gelation of small molecule amorphous drugs

Compared with crystalline drugs,their amorphous forms present long-range disordered molecular arrangements,and often exhibit higher apparent solubility and dissolution.However,several small molecule amorphous drugs may exhibit gelation phenomenon during the dissolution process,and show abnormal dissolution behavior with significantly lower dissolution than crystalline drugs.The current study aims to discover the relationship between the gelation of amorphous drugs and their abnormal dissolution,and further explore the internal gelation mechanism.Amorphous simvastatin(SIM),carvedilol(CAR),and irbesartan(IRB)were prepared by melt cooling method and characterized via X-ray powder diffraction(XRPD),differential scanning calorimetry(DSC),and Fourier transform infrared spectroscopy(FT-IR).Gel formation causes the dissolution of these three amorphous drugs to be significantly lower than their crystalline state.The formed gels were characterized as threedimensional dense network structures by scanning electron microscope(SEM).Furthermore,amorphous SIM,CAR and IRB showed the critical gel temperature at 8-15℃,25-30℃and 45-50℃,and amorphous CAR and IRB showed the critical gel pH at 1 and 0.25.The mechanism of gel formation was proposed to be closely related to the transformation of amorphous drugs into the supercooled liquid state(as the important driving force)and the protonation induced self-assembling under acidic conditions.In addition,the wettability and properties of amorphous drugs also affect the formation of gelation.