Investigation Of Lapatinib Ditosylate Solid Disersion

Lapatinib Ditosylate is a small molecular targeting drug,it has inhibitory effects on the two targets of epidermal growth factor rece-ptor（EGFR）and human epidermal growth factor2（HER2）.But its poor solubility in water leads to low bioavailability.The present study was carried out with solid dispersion technology to enhance the solubility and dissolution rate,so as to enhance the bioavailability of lapatinib ditosylate.Firstly we prepared lapatinib（LA）Ditosylate（DI）solid dispersion（SD）by hot melt extrusion（HME）,Solid state characterization of SD was evaluated by XRD,DSC,SEM and IR.Secondly,we prepar ed the SD of LA-DI by Solvent Rotary Evaporation（SRE）,and its solution/dissolution properties was characterized,the mechanism of solubilization was studied by physical characterization analysis.In the study of SD made by HME,process parameters of HME（including the dosage of soluplus^?,temperature of hot melt,mixing time,screw speed and plasticizer）were optimized.The results showed:the solubility of the extrudate was 17.3 folds higher than that of LA-DI,when the ratio was 1:3:1（LA-DI:soluplus^?:poloxamer）,the extrusion temperature was 160?C,and the mixing time was 10 min.The dissolution was 15.8 folds（pH1 medium）and 20%（2%Tween pH1 medium）increased than that of LA-DI respectively.The results of XRD,DSC and SEM indicated that there were still crystal characteristics in extrudate.IR spectra showed that the peak of LA-DI was smaller and blunter at 1265 cm^-1（C-O）,indicating that the bond was formed between LA and carrier.The results showed that the preparation of SD by HME could destroy the crystallinity of LA-DI to a certain extent,some of LA-DI existed with amorphous,thus the solubility and dissolution were significantly improved.In the study of SD made by SRE,The effects of drug loaded ratio and plasticizers were investigated,The solubility of LA-DI/soluplus^?SD（1:3）was 0.1913 mg/mL（according to LA）,26.3 folds higher than that of LA-DI.The results also indicated that plasticizer had solubilization effect on drugs.The dissolution of SD made by SRE was 22.03%（pH1 medium）and 98.62%（2%Tween pH1 medium）,50.2 folds and 50%increased than that of LA-DI respectively.The results of XRD,DSC and SEM analysis indicated that most of the LA-DI in the SD existed as amorphous state and the others was microcrystals.Moreover,IR spectra indicated that hydrogen bond was formed between LA-DI and the carrier.The results suggested that solid dispersion technology can enchance the solubility and dissolution rate of LA-DI to a certain extent.