Release Behavior And Performance Of Drug-ordered Aggregates

Natural polyphenols drug have excellent anti-oxidation, anti-aging and anti-tumor effect,which have attracted great attention on the food and drug fields, but the disadvantages such as low solubility, poor stability and easy to be oxidized,limited its practical application. Lyotropic liquid crystal as a drug carrier is not only has a green, low toxicity, good compatibilization, good biocompatibility, high biodegradation, physiological activity, but also has a strong effect of slow release and controlled release and protection of drugs. Therefore, natural polyphenols drug was encapsulated in lyotropic liquid crystal. Controlled release and performance of it was studied. This thesis mainly includes the following four parts:(?) This thesis mainly refer to the relevant literature in the earlier stage.Surfactant aggregation as a drug carrier had been comprehensive understood at present. This thesis also expounds the application of surfactant aggregation as drug carrier and research progress of drug release. In this thesis, combining the basis of the original work in laboratory, we found that apigenin and curcumin have similar structural characteristics. Based on the related literature, we found that PEG 400 which was collected in FDA have a good solubilization to apigenin. Therefore we have chosen two lyotropic liquid crystals with PEG 400 to encapsulate apigenin. We are trying to solve the defects, which is the solubility of apigenin is extremely low.And then through the rheological properties and in vitro release experiments to establish the relationship between structure and performance. With a variety of mathematical model, we are simulated on the in vitro release kinetics and founded that the release of apigenin is controlled by concentration. Based on the related literature, we found that Tween 80 and isoamyl acetate have a good soiubility for dihydromyricetin. We chose the lyotropic liquid crystal which was made up of them to encapsulate dihydromyricetin, and we attempt to solve the poor thermalstability of dihydromyricetin and hypersensitivity to light. Furthermore there was a slow-release effect of drugs.(?) In the first place, this text use hexagonal phase lyotropic liquid crystal and lamellar lyotropic liquid crystal, which contains PEG 400, to encapsulate the apigenin. The solubility of apigenin was greatly improved. After that, its rheological properties was studied using rheological technology. We also studied the release behavior in vitro release experiments. The results about the Hexagonal crystal showed as follows:(a) The structure hexagonal phase lyotropic liquid crystal containing apigenin,at 25, 30, 35 and 40 oC, is still maintained a good hexagonal crystal structure.(b) Steady-state rheological properties showed obvious phenomenon of shear thinning, and with the increase of temperature, shear rate under the same shear viscosity decreased.(c) In different temperatures, although LCD type has not changed,but viscous modulus and elastic modulus ratio(tan ?), then decreases, finally has increased.(d) Under the different temperature in vitro release experiments show that when the hexagonal phase liquid keeps good structure, tan ? value greater, the cumulative release rate is smaller.(e) Hexagonal phase liquid in vitro release mainly diffusion control. Lamellar liquid crystal:(a) Unlike hexagonal crystal, the lamellar liquid crystal is mixed phase when below 40 oC. With the increasing temperature of mixed phase of hexagonal phase liquid crystal, the hexagonal phase liquid gradually to the layered phase transition. And then in less than 55 oC under maintained a relatively pure lamellar liquid crystal.(b) Under the different temperature, the temperature of the in vitro release of lyotropic liquid crystal is a typical control. The higher of the temperature, the accumulative release rate in vitro, the faster release rate.(?) With the cubic phase of lyotropic liquid crystal contained the apigenin,rheological properties of lyotropic liquid crystal were studied under the condition of different temperatures. The vitro release behavior of the same LLC at different temperatures and different LLCs in the same temperature were studied. Therheological experiments show that shear viscosity of LLC containing apigenin decreases with the increasing in temperature,. LLC containing apigenin showed obvious shear thinning at 25?30 and 35 oC. It is a typical non-newtonian fluid. It has two obvious Newton platform under lower or higher shear rate at 40 oC. It is a typical Newtonian fluid. Frequency scan showed that the modulus of elasticity and viscous modulus obviously decreased by several orders of magnitude at 40 oC. It also showed that the characteristic of the micellar solution. Seen from continuous temperature scanning, the cubic phase of LLC were destroyed at about 35.7 oC. Under the premise that maintain good cubic phase liquid, in vitro release experiments shown that the accumulative release rate and release rate were decreased with the increase of tan ?when LLC maintain good cubic phase liquid. The in vitro release rate increases due to the damage of LLC at 40 oC. It is a typical diffusion controlled model.(?) We can use lyotropic liquid crystal that which were made of Tween 80,which had very good solubilization effect on DMY, as a drug carrier. We had studied the rheological properties, in vitro release behavior and the protection of drug effect. For seven package load dihydrogen arbutus pigment samples of different continuous temperature scanning of seven LLCs loading DMY showed that sample the F3 and F7 remains a good original liquid crystal structure, and have higher elastic and viscous modulus. The sample of F3 phase has affluented transition behaviors with temperature.And it can take advantage of this feature of slow-release controlled release drug and effective protection. Steady scans show at different temperatures that, shear viscosity decreases with the temperature rising. After phase transformation, the modulus decreased more obvious. Frequency scans showed that with the increase of temperature, viscoelastic modulus of frequency scanning are reduced under different temperatures. Especially after the phase change, reduced modulus is more apparent.And the curve shape of scanning is changed obviously. F7 hexagonal phase is the viscoelastic modulus maximum of original hexagonal phase containing DMY. Steady state under different temperature scanning showed obvious shear thinning behave.And it is a typical non-newtonian fluid. And with the increase of temperature, shear viscosity decreasing. Frequency scanning, under various temperatures, showed thatthe change trend of viscoelastic modulus is similar. Further, it shows that remains the hexagonal crystal structure well under different temperatures. In vitro release experiments show that the molecular thermal motion is the main influence factors about release in vitro of DMY. And it is diffusion control. The accumulative release rate and release rate increased with the temperature increasing. Stability experiments showed that after the DMY was encapsulated in liquid crystal, the stability obviously improved.