星点设计优化夏枯草滴丸固体分散体的制备工艺及体外评价OA

Objective To optimize the prescription and process parameters of Prunella vulgaris pill using solid dispersion technology based on central composite design-response surface methodology(CCD-RSM),with total flavonoid extract of Prunella vulgaris as the core drug.The aim is to improve the drug dissolution rate and enhance bioavailability.Methods The ultrasonic-assisted solvent extrac-tion method was used to extract the total flavonoids from Prunella vulgaris.The solid dispersion was prepared by the solvent-melting method.Taking dropping distance,liquid temperature,condensing agent temperature,and drug-to-matrix ratio as independent vari-ables,a single-factor experiment combined with a four-factor five-level central composite design test was conducted.The comprehen-sive score"overalldesirability"(OD)composed of pill weight difference and roundness,as well as in vitro dissolution,were used as evaluation indicators to optimize the preparation parameters of the solid dispersion pill.Furthermore,the bioavailability was evaluated through in vivo pharmacokinetic experiments in rabbits.Results The optimized process parameters were as follows:dropping tube diam-eter of 2.5 mm,dropping speed of 20 drops/min,dropping distance of 7 cm,liquid temperature of 80℃,condensing agent temperature of 15°C,and drug-to-matrix ratio of 1:4.After optimization,the cumulative dissolution rate of Prunella vulgaris pill in pH 8.8 phos-phate buffer within 45 minutes reached 89%-92%,with an OD value of 0.88-0.92,and a deviation of±2.22%from the predicted value.Pharmacokinetic data showed that compared with Prunella vulgaris tablets,the Cmax and AUC of the solid dispersion were signifi-cantly increased.Conclusion The CCD-RSM can effectively optimize the preparation process of Prunella vulgaris pill solid dispersion,which exhibits better dissolution performance and bioavailability,and has high clinical application value.