Preparation And Properties Of Baicalin,Silymarin Solid Dispersion

Flavonoids have various pharmacological activities and are widely used in clinical.However,most flavonoids belong to BCS II,with high permeability but low solubility,resulting in poor bioavailability.Solid dispersion(SD)is a system formed by highly dispersive mixing of drugs and carriers,which can significantly improve the solubility and dissolution of insoluble drugs.As excellent solvent,deep eutectic solvent(DES)can selectively dissolve a variety of insoluble substances,and it's safe,non-toxic and biodegradable.In this experiment,poloxam 188 with surface active characteristics was mixed with natural ddeep eueutic solvent to prepare solid dispersions of insoluble baicalin and silymarin,which could effectively increase the solubility and bioavailability of the drugs.By the preliminary screening,the solid dispersion carrier was determined to be composed of the high polymer poloxam 188 and the deep eutectic solvent(choline chloride,erythritol and PEG 400).Taking the content of poloxamer,the mass ratio of each component of DES and the preparation temperature as three factors,the orthogonal experiment of three factors and three levels was designed,with dissolution rate in 5 min as index.Finally,optimal ratio of each component in the carrier and the preparation process of baicalin and silymarin solid dispersion were determined.The optimal preparation process of baicalin solid dispersion was 10.0% baicalin,35.5% poloxamer 188,and the mass ratio of each component in the DES was choline chloride: erythritol: PEG 400=1:1.05:1.5(w:w),and the preparation temperature was 60?.The optimum preparation process of silymarin solid dispersion was 10.0% silymarin,40.5% poloxamer 188,and the mass ratio of each component in the DES was choline chloride: erythritol: PEG 400=1:1.25:2(w:w),and the preparation temperature was 55?.The prepared baicalin and silymarin solid dispersions were characterized in various ways.Fourier infrared spectroscopy analysis(FT-IR)proved that the baicalin and silymarin active pharmaceutical ingredients(API)were mainly combined with the carrier by intermolecular hydrogen bondings.The existence states of baicalin and silymarin in the solid dispersions were characterized by X-ray diffraction(XRD),and differential scanning calorimetry(DSC)was used for the thermal analysis of baicalin and silymarin solid dispersions.The results showed that baicalin and silymarin were highly dispersed in the solid dispersions carrier in an amorphous form,and the compatibility between drugs and the carrier was good.By the particle size distribution testing,the average particle size of baicalin and silymarin SD particles in water were 288.02 nm and 304.80 nm with the polymey disperse index(Pd I)of 0.422 and 0.438,respectively.Compared with bacalin-poloxamer 188 SD(459.16 nm)and silymarin-poloxamer 188 SD(528.34 nm),the particle sizes of the prepared solid dispersions decreased significantly,and they had better dispersion and dissolution in the water.The saturated solubilities of baicalin and silymarin solid dispersions were detectd with water and simulated gastric fluid as solvents.As results shown,the saturated solubilities of baicalin SD were 1385.47mg/L and 144.70 mg/L in the water and the gastric simulated fluid,respectively.The saturated solubilities of silymarin SD were 1674.20 mg/L and 138.38 mg/L in the water and the gastr-ic simulated fluid,respectively.The vitro dissolution results showed that,the cumulative dissolution rates of baicalin SD in 60 min were 95.62% and 84.72% in the water and gastric simulated fluid,respectively.The cumulative dissolution rates of silyamrin SD in 60 min were 88.43% and 65.86% in the water and the gastric simulated fluid,respectively.Compared with baicalin/silymarin-poloxamer 188 solid dispersions and baicalin/silymarin API,the dissolution of the prepared baicalin and silymarin SD was improved significantly wiith higher bioavailability.According to the standards in the pharmacopoeia,the quality of baicalin and silymarin solid dispersible particles was evaluated,with main indicators of molding rate,content,disintegration time,drying weight loss,melting,p H and dispersion(apparent suspension rate),and the results show that the prepared baicalin and silymarin solid dispersible particles met the requirements.Finally,with escherichia coli and staphylococcus aureus as research objects,the antibacterial activities of baicalin and silymarin solid dispersible particles were identified.It showed that the concentration of the drugs was positively correlated with the bacteriostatic effect,which meant that the higher the concentration of the drugs,the stronger the bacteriostatic effects.Thus the process of preparing wouldn't adversely affect the biological activity of baicalin and silymarin.