Influences On Vitro Release And Absorption Of Berberine Hydrochloride In Rats With Different Carriers And Proliposome

Objective The subject is to improve the absorption and oral bioavailability of berberine hydrochloride through the screening of different carrier materials and processes. To prepare four different prescription capsules:berberine hydrochloric ordinary capsule, compound capsule, chitosan capsule and proliposome capsule by the wet granule compression technique,based on the early studies and literatures.Take berberine hydrochloride ordinary capsules for the control, with vitro release and plasma concentration in rats as evaluation index, to compare the four kinds of capsules in vitro release and in vivo absorption. To select carrier material can effectively improve the drug bioavailability, and to provide experimental basis for the new formulation-proliposome can increase the bioavailability of insoluble drugs.Methods (1)Respectively starch,Aucklandia lappa extract and chitosan as carriers materials, prepared three different capsules by the wet granule compression technique. The content of berberine hydrochloride in different capsules was determined by HPLC.(2)Berberine hydrochloride proliposomes were prepared by film-deposition on carriers, the encapsulation efficiency was the evaluation index,the single factor exploration and orthogonal design were used to select the optimum formulation. PBS (pH7.0) as eluent, liposomes and free drug was separated by SephadexG-50gel column chromatography,10%Triton X-100solution as broken membrane agent.The encapsulation efficiency was determined by HPLC.The physicochemical properties of proliposome and preliminary stability were investigated.(3)A basket method was used to study the dissolution of four different capsules in artificial gastric juice and in artificial intestinal juice.The accumulative release of the drug was mimicked with release model equations, and similarity estimation.(4)The berberine in rat plasma was determined by RP-HPLC,the plasma concentration of berberine hydrochloride in four different capsules after oral administration in rats were determined,the pharmacokinetic parameters were calculated with software Kinetica4.4and analyzed by one-way ANOVA and multiple comparison with SPSS16.0.Results (1)in vitro release experiments showed that, the release of berberine hydrochloride in the three different capsules as follows:compound capsule release slowly in artificial gastric juice, the release of chitosan capsules is the fastest; berberine compound capsules and ordinary capsules release similarly in the artificial intestinal juice, chitosan capsules have a unique release curve, the release of berberine is faster. The results showed that,chitosan can promote the dissolution of berberine hydrochloride release.(2)Pharmacokinetic studies showed that,the pharmacokinetic parameters of three kinds of capsules have no obvious differences except peak time. Aucklandia lappa extract cannot promote the absorption of berberine, chitosan can promote the dissolution and absorb of berberine, could increase the plasma concentration and shorten the peaktime, elimination also accelerated, but the oral bioavailability did not improve.(3)Liposomes as a new carrier, the optimum preparation process as follows:the ratio of phospholipid to drug was8:1,the ratio of phospholipid to cholesterol was4:1,the ratio of carrier to phospholipid was2:1.The three batches of berberine hydrochloride proliposomes were light yellow particles and have good fluidity. The angle of repose was34.8,the encapsulation efficiency was38.68%,the average particle size was741.9nm.The preparation technology was stable and reliable. The result of stability test showed that the berberine hydrochloride proliposomes were better stable under high temperature conditions, unstable under high humidity and lighting conditions.It should be protected from light, moisture when storage and transport.(4)The release of proliposomes in vitro is slower, showed an sustained release effect. The cumulative release of berberine hydrochloride was41.7%in20hours in artificial gastric juice, the release model match to the Higuchi equation, and was84.1%in20hours in artificial intestinal fluid, the release model fitted to the Weibull equation.(5)The bioavailability of berberine hydrochloride proliposomes relative the ordinary capsules was123.7%, relative the blank proliposomes was157.72%.and there are significant differences (p<0.05),compared with the first three capsules, bioavailability were1.24times of the ordinary capsules,1.58times of the compound capsule and1.6times of the chitosan capsules. Indicating that proliposome can improve the absorption of berberine in vivo and oral bioavailability.Conclusions Compared the release of four different berberine hydrochloride capsules in vitro and pharmacokinetic changes in vivo, found that chitosan as a carrier material can promote the dissolution and absorption of berberine, but not significantly increase the bioavailability.The new formulation proliposome can promote the release of berberine and can significantly improve the bioavailability of berberine in vivo. And proliposomes is solid, can avoid hydrolysis,precipitation, aggregation and drug leakage of liquid liposomes, and improve the stability of the liposomes。...