Study On Preparation Of Itraconazole Solid Dispersion By Hot Melt Extrusion Technology

Hot melt extrusion technology is an emerging technology for the development of insoluble drugs in the domestic pharmaceutical field in recent years.It has the advantages of no organic solvent addition,online control,continuous production,easy amplification and no dust.It has the advantages of no organic solvent addition,online control and continuous production,and easy amplification.In this study,the insoluble drug Itraconazole solid dispersion was prepared by hot melt extrusion method,and its dissolution in vitro was improved by various techniques to be used for its solubility and bioavailability problems.Objective: Itraconazole is a clinically used triazole antifungal for fungal infection.Currently,200 mg tablets are sold in the United States and Japan in the international market,and are prepared by hot melt extrusion technology.Due to the level of preparation and the like,there is no corresponding tablet in the domestic market.Therefore,the research on the preparation of itraconazole solid dispersion by hot melt extrusion technology contributes to the development of itraconazole tablets.Method: 1 Preformulation study.Investigate the current prescriptions and processes of commercially available products.For the thermal analysis of itraconazole and its excipients,the compatibility between itraconazole raw materials and excipients and different carriers was investigated.A linear equation of absorbance and concentration and an in vitro dissolution method were established.2 Thin film method to screen the carrier ratio.Using HPMC E5 as the carrier,the effect of drug loading and drug loading on the glass transition temperature was screened by thin film method,and a linear curve was established.3 hot melt extrusion technology to prepare itraconazole solid dispersion.Comparison of various process methods,selection of the best suitable formulation process for characterization.Results: 1.The basic prescription process was determined through information research,and HPMC E5 was used as the carrier to prepare by hot melt extrusion technology.2.The drug loading of 40% was screened by the thin film method,and the phase transition was found as a new auxiliary method for determining the drug loading andsolubility.3.Different hot melt extrusion processes have different degrees of dissolution results.The use of propylene glycol and water mixed solvent as plasticizer not only improves the state of the extrudate but also improves the dissolution in vitro,which is 10%PG granulation extrusion > 5% PG granulation extrusion > secondary extrusion > direct extrusion > physical mixing.