Study Of Baicalin Percutaneous Penetration Properties And Its Transdermal Delivery Systems

Transdermal drug delivery system (TDDS) is a rapidly developing topic inpharmacy in these years. The design and preparation of the TDDS involve four keyfactors: the medicines, carriers, transdermal enhancers and pharmacology. In thisthesis we focused on the baicalin transdermal properties and its exterior preparations.Firstly, a method of HPLC was set up to determine baicalin quantitatively. Theoil/water partition coefficient (P) and pKa were measured. The data indicated thatbaicalin is a kind of subacid drug and the P of baicalin decreases when the pH value isincreased. The solubility and stability of baicalin in different solvents are investigated.It is found that the baicalin is unstable when the concentration is low and the aqoussolution pH value of is above 7.0.The results show that the baicalin solution is stablewhen the concentration is 100mg/ml and the stability varied little when changing thepH value from 6.0 to 8.5. It is found that the baicalin solution even in lowconcentration of PEG400/brine (40%:60%) is very stable. Hence in this thesis weused PEG400/brine (40%:60%) combinated solution as the receptor solution in the invitro drug transdermal delivery experiments. Secondly, in glycerol-propanediol-ethanol solution, transdermal enhancers wereemployed to improve the skin penetration amount of baicalin. The results showed thatthe skin penetration amount of baicalin increased when the concentration of azonewas raised. But when the azone concentration is over 10%, the baicalin skinpenetration amount decreased. The retardation time of azone was about 2 hours andcould be shorted by co-using the oleic acid. The maximum penetration amount ofbaicalin was obtained by using a combination of azone and oleic acid in the ratio of10%:0.5%. In the other hand, in aqous solution the transdermal property of baicalin inthe alkalin solvent was better than in the acidic solvent. Chitosan with molecularweight 3000-5000 was added to the baicalin solution. The results showed thatchitosan could enhance the baicalin percutaneous delivery rate and this enhancementvaried with the pH value and the chitosan concentration. XPS was applied to study theenhanced mechanism of chitosan. The results indicated that there should be aninteraction between the chitosan and baicalin.Thirdly, three baicalin TDDS (patch, gel and ointment) were designed andprepared. The results showed that all these three TDDS have good baicalintransdermal delivery properties. Among them, the skin penetration amount of baicalinpatch was the highest.The last focus of this thesis was on the pharmacokinetics of baicalin drippingpills, patches and ointments. The metabolism of baicalin dripping pills and patchesaccord with two-compartment model with 1st order absorption, and the metabolism ofbaicalin ointment accord with one-compartment model with 1st order absorption. Byusing the baicalin patches, the absorption and elimination of baicalin was slower thanusing the baicalin dripping pills. This means that the baicalin patches could havepotential clinical application.