A Preliminary Study On The Preparation Technology And Pharmacokinetics Of Freeze-dried Orally Disintegrating Tablets Of Ginkgo Biloba Extrac

Objective:Establish the preparation method of freeze-dried oral disintegrating tablets of Ginkgo biloba extract;correct the bitter taste of Ginkgo biloba extract to improve its bad taste;optimize the prescription,preparation process and freeze-drying curve of freeze-dried oral disintegrating tablets of Ginkgo biloba extract.Prepare the tablets with excellent shape,rapid disintegration and easy storage;study the pharmacokinetics of freeze-dried oral disintegrating tablets of Ginkgo biloba extract in order to provide reference for follow-up clinical research.Methods:Taking the comprehensive evaluation table,high performance liquid chromatography,fingerprint spectrum and scanning electron microscope as the evaluation index,the evaluation system was established to determine the amount of main excipients in the lyophilized tablets of Ginkgo biloba extract.The key process and freeze-drying curve in the preparation process were optimized.The pharmacokinetic parameters of freeze-dried ginkgo biloba extract tablets were studied by sublingual and intragastric administration in Beagle dogs and Ginaton extract tablets as reference preparation,and its bioequivalence was evaluated.Results:(1)in the ginkgo biloba extract,the contents of total flavonoids,terpene lactones and ginkgolic acids all meet the requirements of the Pharmacopoeia.After the Ginkgo biloba extract was prepared into freeze-dried oral disintegrating tablets,the total flavonol glycosides lost 6.20%and terpene lactones lost 19.84%.After the preparation of oral disintegrating tablets,the content of effective components still conforms to the relevant regulations.(2)the optimized formulation of freeze-dried ginkgo biloba extract tablets is:ginkgo biloba extract 40mg/tablets,pullulan polysaccharide 15.00mg/tablets,mannitol 9.00mg/tablets.The preparation process is as follows:the raw and auxiliary materials are weighed in a shear cup according to the prescription,dried and evenly mixed,then purified water is added to fix the volume,and the solution is stirred on a magnetic agitator to make the raw and auxiliary materials disperse in the aqueous solution,then the 5min is cut at a speed of 2500 r·min-1 by a high shear mixing emulsifier,and the solution is degassed and packed into a bubble cover with a liquid transfer gun,which is pre-frozen in the refrigerator at-60℃.The freeze-drying curve is:-25℃ into the box,maintenance time 10 min,rising temperature to-15℃,heating time 10min,maintenance time 90 min,heating up to 25℃,heating time 40min,maintenance time 60min,film-coated packaging.It is verified that the oral disintegrating tablets prepared in the experiment have good repeatability.(3)the bioequivalence of 7 active components in Ginkgo biloba extract was analyzed by UPLC-MS/MS.The pharmacokinetic parameters of positive drug and oral disintegrating tablet group,positive drug oral disintegrating tablet sublingual administration group,oral disintegrating tablet sublingual administration group and oral disintegrating tablet sublingual administration group were analyzed by UPLC-MS/MS.The results showed that there was no bioequivalence between the two preparations and different administration methods.Among them,oral disintegrating tablets intragastric administration and sublingual administration,the AUC of seven active components were larger than the corresponding data of positive drugs.Conclusions:The main results are as follows:(1)the methods of content detection,comprehensive score and microstructure observation of ginkgo biloba extract and oral disintegrating tablets were established to provide reference for the quality evaluation of freeze-dried ginkgo biloba extract tablets.(2)the preparation process of freeze-dried oral disintegrating tablets of Ginkgo biloba extract is stable and feasible.the prepared oral disintegrating tablets have good appearance,rapid disintegration,qualified water content,uniform content,small weight difference,small loss of effective components,full micro-skeleton structure and orderly arrangement.(3)after oral administration and sublingual administration of ginkgo biloba extract tablets and oral disintegrating tablets,there were significant differences in AUC,and there was no bioequivalence.According to AUC,it was found that the absorption of oral disintegrating tablets was superior to that of common tablets,and the results of sublingual and sublingual administration of ginkgo biloba extract showed that AUC was significantly higher than that of sublingual tablets,and the effective components of ginkgo biloba extract were partially absorbed by mucosa.In addition,compared with ordinary tablets,oral disintegrating tablets have their own advantages,such as convenient to take,improve patient compliance and so on,so making ginkgo biloba extract into oral disintegrating tablets has a certain practical significance.