The Preparation and Pharmacokinetic Studies of Neiyixiao Sustained-release Capsule
|Keywords||Endometriosis Sustained-release hot fusion method Ferulic acid Hydrochloric ligustrazine Tetrahydropalmatin|
ObjectiveTo establish a method that can insure the ferulic acid, hydrochloric ligustrazine and tetrahydropalmatine in the prescription to reach susutained release effect and evaluate the susutained release effect in vitro and in vivo.Methods1. Preparation of Neiyixiao sustained-release capsules The effects of different excipients about water-soluble sustained release excipient H, insoluble sustained release excipients EC and erodible excipients such as O, M, S and G were investigated; Though the single factors experiments,A Box-Behenken model was established to optimize the factos,the cumulative release of2h,6h and12h of three drug in Neiyixiao were optimization index.2. Quality control of Neiyixiao sustained-release capsules According to the Pharmacopoeia,the content, loading difference, particle size, related substances, identification were investigated to control the quality of the capsules, the quality standards draft of Neiyixiao sustained-release capsule was established.3. Stability of Neiyixiao sustained-release capsules The Sustained-release capsule were taken under the factor experiment, the accelerated experiment and the long-term experiment to study the stability of the product.4. Pharmacokinetics of Neiyixiao sustained-release capsules in rats The method detect the three substances in vivo were established by HPLC; The rats were intragastric administrated of of bulk drugs and capsule at the dose of180mg/kg, the plasma was tested by HPLC to detect the drug at different time after administration. The pharmacokinetic parameters were analysised by DAS softwere.Results1.Preparation of Neiyixiao sustained-release capsules The preparation method was established:At the drug and xcipients are x, H and G are y, the drug and H were added to the molten G accompanyed with stirring, the compound were cooled after30min in room temperature,sieved and capsuled.2.Quality control and stability of Neiyixiao sustained-release capsules (1) At the condition of methanol-0.5%acetic acid (42:58) as the mobile phase,280nm as detection wavelength. The content of ferulic acid, hydrochloric ligustrazine and Tetrahydropalmatine were all at the90～110%as to the labeled amount (2) Load difference<±7.5%.(3)The particle size was controlled with in90%between60mesh and80mesh.(4) The cumulatived release of ferulic acid in2h,6h,12h should meet10～20%、60～70%、90～100%; The acumulatived release of f ligustrazine hydrochloride in2h,6h,12h should meet the35～45%,60～70%,85～95%; The acumulatived release of tetrahydropalmatine in2h,6h,12h should meet20～30%,55～65%,80～90%.3.Stability of Neiyixiao sustained-release capsules Stability results showed that humidity was the important factors among the three factors. It’s content, related substances and release were relatively stable in the accelerated experiment in three month.3. Pharmacokinetics of Neiyixiao sustained-release capsules in rats:(1) At the condition of methanol-0.5%acetic acid (38:62) as the mobile phase,280nm as detection wavelength and Coumarin as internal standard,the drug effective ingredients all had a good liner relationchip,the method was good for the determination them in plasma with a good precion and recovery.(2) From the pharmacokinetic experiments in rats, the t1/2of ferulic acid, hydrochloric ligustrazine and Tetrahydropalmatine were2.31、2.53、2.62times as to buik drugs; the Tmax of the three drugs were extend from the0.52h to3.25h, from the0.46to2.5h, from the0.46h to2.5h, and the AUC were2.1、1.25和1.85tims to the bulk drugs.Conclusion:The Neiyixiao Sustained-release capsule prepared by melt granulation was proved to have a sustained effect in vitro and in vivo, and the quality control and stability experiment proved it’s a simple and easy to control preparation.