The Preparation And Properties Characterization Of Trimethopprim Solid Dispersion And Inclusion Complex

Trimethopprim（TMP）is a kind of broad spectrum, high efficiency, low toxicity ofantimicrobials, mainly considering as a synergist of sulfonamide. It is used as feed addtiveswhile treating bacterial infections in poultry、livestock,etal. But the TMP is almost insolublein water, the absorption is poor and bioavailability is low. Mixing unevenly or diet will affectthe efficacy of the drug. It is convenient to deliver drug by drinking water if the drug isdeveloped into a powder.Also it can prove absorption and bioavailability.Emulsified TMPSold on the market is soluble in water, But while mixing with SMM-Na，it appears milkyand Turbid, Greatly influencing the exertion of efficacy. In this paper, solid dispersion andpackage technology with a series of research has been used to improve the solubility ofTMP,futher solve the solubility problem of TMP and SMM–Na in aqueous solution.In this paper, the solid dispertions were prepared by using melting and solvent methodwith PEG4000-PEG6000, PVP as the carrier respectively. The results of solubility ofTMP-SD and the effect of TMP-SD dissolved in water with SMM-Na has conducted todetermine preparation conditions: Melting method with PEG4000-PEG6000as carrier, Theratio of drug-carrier is:1:2:5, The preparation temperature is110℃. Solvent method withPVP as carrier, the ratio of drug-carrier is1:6, the preparation temperature is80℃, thepreparation time is4h. Results of solubility experiment showed that，the solubility of TMPsolid dispersion has been proved significantly:The solubility of TMP-PEG4000-PEG6000SDwas up to6.16mg/mL and TMP-PVP SD was5.03mg/mL, aqueous solution with TMP-SDand SMM-Na keeps clear and transparent within6hours, The dissolution of solid dispersionis increased accordingly，compared to raw materials.In this paper,the TMP inclusion complex withβ-cyclodestrin(β-CD) was prepared bystaturated aqueous solution method，The results of solubility of TMP-SD and the effect ofTMP-SD dissolved in water with SMM-Na has conducted to determine preparation conditions:aqueous solution which contained2%acetic acid as solvent, PVP as carrier, The inclusionmolar ratio of drug-carrier is:1:1, The preparation temperature is80℃，stirring time is3h,and the samples were washed3times with0.01mol/L NaOH-absolute ethanol rapidly toremove acetic acid. Results of solubility experiment showed that，the solubility of TMPinclusion complex has been proved significantly:The solubility of TMP-β-CD inclusioncomplex was up to5.26mg/mL, aqueous solution with TMP-SD and SMM-Na keeps clearand transparent within6hours, The dissolution of inclusion complex is increasedaccordingly，compared to raw materials. The results of uv absorption showed that TMP solid dispersion or inclusion complexwere consistent with TMP and they were physical combination between TMP and carrier.Theresults of differential scanning calorimetry (DSC) and scanning electron microscope (SEM)showed that TMP was dispersed or existed in the form of crystallites in SD and TMP existedin the form of molecular in inclusion complexes.The solubility and dissolution of TMP-SDand TMP inclusion complex were significantly increased due to the increased ratio of surfacearea.The results of Stability and long-term experiments showed that the preparation of TMPsolid dispersion or inclusion complex has yet to be further optimized.