Preparation And Evaluation Of Total Phenol Of Magnolia Solid Dispersions

This research prepared total phenol of Magnolia solid dispersion by hot-melt extrusion to study the application of this technology in improving dissolution and bioavailability of insoluble component by prepared Multi-component of Chinese herbal medicine solid dispersion and investigate the advantages of this technology in preparing Multi-component of Chinese herbal medicine solid dispersion.Total phenol of Magnolia belongs to the lignin compounds,is the effective active site derived from Magnolia officinalis Rehd.et Wils,the main efficacy ingredient are honokiol and magnolol,which have a special,long-lasting muscle relaxation and strong antibacterial effect,also they can inhibit platelet aggregation and the major resulting in the low bioavailability,which limiting the clinical application.TPM belongs to the lignin compounds,is the effective active site derived from Magnolia officinalis Rehd,et Wils,the main efficacy ingredient are honokiol and magnolol,which have a special,long-lasting muscle relaxation and strong antibacterial effect,also they can inhibit platelet aggregation and the major clinical are used as antibacterial.But due to the poor water solubility of TPM,the bioavailability is very low,which limiting the clinical application of TPM.By thermal gravimetric analysis,it was confirmed that main efficacy ingredient magnolol and honokiol of TPM could be remain stable at 120? which provide a reference for the set up of the hot-melt extrusion process parameters.The equilibrium solubility in water of magnolol and honokiol is 39.13 ?g/mLand 8.32 ?g/mL respectively determined by Classic shake-flask method,it shows that magnolol and honokiol have a strong hydrophobicity.We establish a convenient,fast and stable method to determine the content of magnolol and honokiol in rat plasma by UPLC-MS/MS tandem technology,the results of pharmacokinetics research show that absolute bioavailability of magnolol and honokiol is 18.62%and 7.80%respectively.clinical are used as antibacterial.But due to the poor water solubility of TPM,First we prepared magnolol solid dispersion by hot-melt extrusion techniques,the solubility parameters of magnolol was calculated to be 24.27MPa1/2 by the group contribution method using molecular modeling pro software,basis on it,we screened out four new polymers of Plasdone S-630,HPC,Eudragit EPO and Soluplus at different ratios of 1:3,1:6 and 1:9 for the extrusion process.The physico-chemical characterizations were performed with in vitro dissolution studies,differential scanning calorimetry(DSC),X-ray powder diffraction(XPRD),Fourier transform infrared(FT-IR)spectroscopy.Based on the data in vitro,Plasdone S-630,HPC and Eudragit EPO at ratio of 1:6 were selected for in vivo pharmacokinetic studies.Comparing to the untreated Mag coarse powder and the physical mixture with polymers,the solid dispersions prepared with Plasdone S-630 or HPC(drug/polymer:1:6)showed a significant enhancement of Cmax(approximately 5-fold and 2.3-fold respectively)and AUC was increased approximately 37.22%and 70.88%respectively,but the solid dispersion prepared with Eudragit EPO could not improve the bioavailability of magnolo.Thus the suitable dispersing medium for preparing magnolol solid dispersion are Plasdone S-630 and HPC.According to the results of monomer,the polymers Plasdone S-630 and HPC were applied to prepare TPM solid dispersion and the hot-melt extruder could work well.The in vitro dissolution research showed that the dissolution rate and extent of magnolol and honokiol were significantly increased compared with API.And differential scanning calorimetry(DSC),X-ray powder diffraction(XPRD)and fourier transform infrared(FT-IR)spectroscopy verified the amorphous solid dispersion were prepared.The in vivo pharmacokinetic studies also show the bioavailability of active ingredients were significantly increased.According to the results,we infer that the mature ideas and methods of preparing monomer solid dispersion could be successfully applied to Multi-component of Chinese herbal medicine.To compare the difference between hot melt extrusion technology with the traditional solid dispersion preparation technology.Hot melt extrusion,solvent evaporation method,Fusion-cooling were used to prepare TPM solid dispersion with Plastone S-630 and HPC respectively.The results of DSC and X-ray diffraction show three solid dispersion process all can prepare amorphous solid dispersion,FT-IR results can not distinguish the difference between the three processes,but show the force between drug and polymer prepared by hot-melt extrusion is stronger than other two methods.Accelerated stability-in vivo dissolution test show the stability of solid dispersion prepared by HPC was better than Plastone S-630,between the same kinds of materials solid dispersion prepared by hot melt extrusion show a better stability than the other two processes.Bioavailability test results showed no significant differences in three solid dispersion preparation methods.So the main advantages of hot melt extrusion technology is suitable for industrial production and the production show a better stability.