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Studies On The Drug Release Kinetics In Vitro And Vivo Of Chuangping Sustained-release Pellets

Posted on:2015-04-02Degree:MasterType:Thesis
Country:ChinaCandidate:Y LuoFull Text:PDF
GTID:2284330452953786Subject:Pharmacy
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The research on evaluation in vitro and in vivo pharmacokinetic of sustained-release preparations of traditional Chinese medicine are limited to the composition ofthe single index method, correlation between in vivo and in vitro slow-releasepreparations of Chinese medicine research lags behind. The topic primarily studies thepreparation technology, multiple target-ingredients in vitro release characteristic andin vivo pharmacokinetic in Chuangping sustained-release pellets, to clarify thecorrelation between in vivo and in vitro, to provide the basis for evaluation in vitroequilibrium release to replace evaluation in vivo equilibrium release of traditionalChinese medicine compound sustained-release preparations.HPLC method is respectively used to establish the content of ephedrine,pseudoephedrine and scopolamine. In the process of preparing Chuangpingsustained-release pellets, blank-pellets are prepared by rapid mixing granulation andcoated pot spheronization. The core roundness, bulk density, friability and yield ofblank-pellets as the index, screen the best prescription of preparation of blank pillwhich is prescription four. The Chuangping pellets are prepared by fluidized bedcoating method. Screening the Chuangping pellets prescription,the factors such asdrying temperature,spray pressure, rotating speed of peristaltic pump which areinfluenced on the prescription are investigated.Based on the orthogonal test,the yieldof chuangping pellets is regarded as the evaluation index to screen out the bestprocess parameters. The optimum prescription selected out is prescription6.The best process parameters of preparation pelltets are as follow: the drying temperature is T3℃, atomization pressure is B3bar, peristaltic pump is R2rpm.In the coating processof Chuangping sustained-release pellets, take the release rate as the inveatigate indexto screen out the slow release film coating liquid prescription, the factors such asdrying temperature,spray pressure, rotating speed of peristaltic pump which areinfluenced on the prescription are investigated. Based on the orthogonal test,theadhesion conditions, atomization pressure,clothing membrane integrity,clothingmembrane integrity and coating efficiency are regarded as the evaluation index toscreen out the best coating process parameters. The optimum coating prescriptionselected out is prescription4.The best coating process parameters are as follow: thedrying temperature is t2℃, atomization pressure isb2bar, peristaltic pump is r2rpm.Inaddition, investigating the factors which influence in vitro release degree, when thecoating weight is15%, auxiliary materials3is the pore former, the proprtion of poreformer is7.14%in the polymer, the Chuangping sustained-release pellets has goodslow release effect. Regarding ephedrine, pseudoephedrine and scopolamine asindicators,it is to research in vitro release behavioro of Chuangping sustained-releasepellets, through the in vitro drug release curve fitting the drug release model, andcombining stereo microscope and biological microscope to evaluate its drug releasemechanism. The results show that ephedrine and pseudoephedrine and scopolaminefollow drug release level model, the drug is mainly given with diffusion,accompanying by skeleton corrosion. At the same time, it also state that Chuangpingsustained-release pellets is membrane diffusion control.The Chuangping sustained-release pellets of single doses are orally administratedto beagle dogs. Ephedrine, pseudoephedrine and scopolamine are regarding as theindex ingredients, UPLC is used to determinate the blood drug concentration of thesethree components. The pharmacokinetic software DAS3.1.1is used to calculate thepharmacokinetic parameters, and fit the compartment model. Ephedrine,pseudoephedrine and scopolamine accord with the single compartment model inBeagle dogs.The calibration cure of ephedrine is linear in the range of0.003~0.087μg,the method recovery is greater than95%,the inter-day and intra-day RSD are all less than10%. The main pharmacokinetic parameters of ephedrine are as follows: AUC(0-t)is (44.18±0.88) μg·ml-1*h,AUC(0-∞)is (49.98±1.88) μg·ml-1*h,t1/2is (7.29±0.39) h,Tmaxis (2.50±0.00) h, Cmaxis (4.04±0.05) μg·ml-1, V is (4.89±0.08) L, CLis(0.47±0.02) L·h-1.The calibration cure of pseudoephedrine is linear in the range of0.0040~0.1011μg, the method recovery is greater than95%,the inter-day andintra-day RSD are all less than10%. The main pharmacokinetic parameters ofpseudoephedrine are as follows: AUC(0-t)is (15.87±0.15) μg·ml-1*h,AUC(0-∞)is(17.98±0.34) μg·ml-1*h,t1/2is (7.34±0.21) h, Tmaxis(2.50±0.00) h, Cmaxis(1.44±0.02) μg·ml-1, V is(4.68±0.05) L, CL is(0.45±0.01) L·h-1. The calibration cureof scopolamine is linear in the range of0.0005~0.0597μg, the method recovery isgreater than95%,the inter-day and intra-day RSD are all less than10%. The mainpharmacokinetic parameters of scopolamine are as follows: AUC(0-t)is (7.05±0.12)μg·ml-1*h, AUC(0-∞)is (7.75±0.19) μg·ml-1*h,t1/2is (6.34±0.31) h, Tmaxis(2.50±0.00)h, Cmaxis(0.67±0.01) μg·ml-1, V is(4.72±0.12) L, CL is(0.52±0.01) L·h-1. The UPLCmethod established can be used for the blood drug concentration determination andpharmacokinetic study of ephedrine,pseudoephedrine and scopolamine.Wagner-Nelson method is used to study the correlation between in vivo and invitro of Chuangping sustained-release pellets, The correlation coefficients in vivo andin vitro of ephedrine, pseudoephedrine and scopolamine are respectively0.9911,0.9953and0.9735. There is good correlation between in vivo and in vitro ofephedrine, pseudoephedrine and scopolamine. It can use equilibrium releaseconditions in vitro to predict equilibrium release behavior in vivo.
Keywords/Search Tags:Chuangping sustained-release pellets, preparation technology, relesaedegree in vitro, pharmacokinetic, in vitro-in vivo correlation
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