Primary Solidification Study Of Phospholipid Complex For Magnolol

The process of drugs into the body can roughly be divided into absorption,distribution,metabolism and elimination in pharmacy,namely ADME process.Absorption is the first and most important process,but it can be affected by many factors,like first-pass effect,solubility,membrane permeability and so on.Through literature research we find that:magnolol has great pharmacological effects in magnolia.However,the poor solubility causes the low oral bioavailability,which has indirect impact on the clinical use.Thus,in this study,we apply the solidification technology to the drug-phospholipid complex,which can improve the solubility of poor drugs.The followings are specific research contents:1.Studies on magnolol's equilibrium solubility and oil-water partition coefficientIn this study,magnolol's equilibrium solubility was measured in different solvents like water,methanol,ethanol and phosphate buffer solution at different pH,while oil-water partition coefficient was also determined in phosphate buffer solution at different pH.The results showed that magnolol's equilibrium solubility was about 20 times in organic solvents than in water,and it has pH independent character.pH had little difference in oil-water partition coefficient ranging from 4.6-5.3.2.The preparation and characterization of magnolol phospholipid complexIn this chapter,magnolol and phospholipid were weighted at the mass ratio of 1:1,10.0 mL anhydrous ethanol was added to dissolve them,then stirred for 2 h,solvent should be removed before we got the semisolid with rotary evaporates.The characterization of the magnolol phospholipid complex also be evaluated.The scanning electron microscopy(SEM)results showed that the crystal structure of magnolol in the magnolol phospholipid complex was completely disappeared and the amorphous shape was presented.The differential scanning calorimetry(DSC)results showed that the characteristic absorption peak disappeared in the magnolol phospholipid complex,indicating that the drug was in amorphous state.The infrared spectrum(IR)analysis suggested that the substances in the magnolol phospholipid complex of magnolia didn't form new bonds or simply physical mixed,which might be combined by intermolecular forces.3.The selection and optimization of materials with phase characterization for samplesPVPP(polyvingypyrrolidone)was determined as the best material by dissolution test in this chapter.The suitable mole ratio of magnolol,phospholipid and PVPP was 1:1:2.The cumulative dissolution rate of solidified magnolol phospholipid complex with PVPP powder within 60 min in dissolution medium at pH 2.0 and 6.8 were 89.32%,91.39%,respectively.What is more,these were higher than that of magnolol phospholipid complex(in the same conditions,the cumulative dissolution within 60 min were 82.23%and 80.23%,respectively,(P?0.05).In this condition,the dissolution medium of pH 6.8 had higher cumulative dissolution rate,however,it had no statistical significance.The scanning electron microscopy(SEM)results showed that the crystal structure of magnolol in the solidified powder was completely disappeared and the amorphous shape was presented.The differential scanning calorimetry(DSC)results showed that the characteristic absorption peak disappeared in the solidified powder,indicating that the drug was in amorphous state.The infrared spectrum(IR)analysis suggested that the substances in the solidified powders of magnolia didn't form new bonds or simply physical mixed,which might be combined by intermolecular forces.The angle of repose was 31° measured by flowing test,posing more advantages for clinical usage and preparation.4.Study on the oral bioavailability of the solidified magnolol phospholipid complex with PVPPThe optimized ratio of PVPP was determined in this chapter to make solidified magnolol phospholipid complex.The oral bioavailability experiment results showed that max plasma concentration was 8.55 ?g·mL-1 in 1.24 h,and the AUC0-? reached up to 73.47 ?g·h· mL-1,while the magnolol phospholipid complex group AUC0-? was 63.48 ?g· h-mL-1.All these results had statistical significance(P<0.05)compared with magnolol phospholipid complex.In conclusion,magnolol phospholipid complex was successfully prepared.The best material and its optimized ratio were determined through dissolution test,which could improve its flow ability to provide convenience for industrial production.Then solidified magnolol phospholipid complex powder was used in rats' oral bioavailability to verify its bioavailability,providing reference for wide clinical application.