Cantharidin And Cantharidin Extracts Of Oral Sustained-release Formulations

The thesis developed some determination method of cantharidin for different aims, such as HPLC, GC, GC-MS. This thesis studied the basic physicochemical characters of cantharidin and the extract of Mylabris, then studied the pharmacokinetics properties of cantharidin in beagle dogs by GC-MS. Prepared solid dispersion about CA and the extract of Mylabris. Then studied the effect of solid dispersion preparation. Using the chitosan as the bioadhesive material and absorption enhancer, the solid dispersion as the media preparation, prepared the cantharidin and the extract of Mylabris bioadhesive drug delivery systems whose pharmacokinetics parameters were studied in SD rats.Firstly, the assaying method of CA was established. On one hand, we perfected the HPLC and GC to assay the CA content in vitro; on the other hand, a simple, sensitive and specific GC-MS method was developed, which could assay CA in vivo. HPLC and GC were used to study physicochemical character of cantharidin and the extract of Mylabris to provide the guaidence to preparation. Then the GC-MS was used in the pharmacokinetic study and evaluate in vivo study. One-compartment model best described the blood level data for CA after intravenous administration and oral admintration. It shows CA eliminate quickly in vivo and has a low oral bioavailability 26.7%. The parameters will provide the theoretic basis for the rational use of CA.Secondly, two kinds of preparations was obtained, used PEG4000 as dispersion carrier which was reported to enhance drug dissolubility and alleviation the stimulatory to gastric mucosa. Then the CA's release curve from two formulations was studied, and it is proved that the effects of the formulation on the release curve of CA were more completely. Then, the bioadhesive particles that using the chitosan as the absorption enhancer and bioadhesive material, the solid dispersion as the media preparation was prepared after the uniform test in order to get the slow release effect.At last, the bioavailability of bioadhesive particles and the two preparations were evaluated in vivo. In the experiment, the pure CA is reference formulation and the other preparations are test formulation. The plasma concentration-time profiles of CA was studied and assayed by GC-MS method. The result indicated that comparing to the CA, CA bioadhesive patricals and Mylabris extract bioadhesive patricals both showed a significant sustained-release effect in rats.