Preparation Solid Dispersions Of Praziquantel And The Pharmacokinetic Study In Dogs

Praziquantel, an anti-trematde and anti-tapeworm broad-spectrum drug, applies to all kinds of schistosomiasis, clonorchiosis, paragonimiasis, taeniasis and cysticercosis, etc. Praziquantel works remarkably for most of both adult tapeworms and immature tapeworms, peeling off worms with the effect of spastic paralysis by means of exposing to tapeworms inside the hosts. And another way of peeling worms off the hosts by Praziquantel is to increase calcium ion level of worms’ muscle cells through affecting calcium ion permeability. Praziquantel is the first medicinal choice in treating schistosomiasis, which seriously does harm to the health of human being and animal, basically because it is featured as good curative effects, low toxicity and secure application.First, in the essay, experiment proposed an analytical method in vitro of Praziquantel. Based on physical and chemical properties and carrier materials of Praziquantel, this essay established appropriate determination methods for content and dissolution rate. Methodology experiments indicated that the mentioned analysis methods are feasible with high specificity and good repeatability.Second, this essay prepared solid dispersions of Praziquantel(PZQ-SD)respectively adopting three approaches of solvent method, melting method as well as solvent-melting method, and chose polyethylene glycol 4000(PEG4000), polyethylene glycol 6000(PEG6000), and poloxamer 188(P188) as carriers, all of which are commonly-used water-soluble materials. Besides, taking data of dissolution rate into consideration, the study evaluated the impact on dissolubility of PZQ-SD under three variable factors of carrier materials, preparation methods and ratio of drugs and carriers.Based on the evaluation, the study determined the best method for preparing PZQ-SD: the quality ratio of praziquantel and combined carriers was 1:5, the quality ratio of PEG 4000 and P 188 was 3:1, and solvent method was used for preparing, ethanol of 950 m L/L as solvent. And then, Praziquantel solid dispersions and physical mixtures would be indentified by X- ray diffraction analysis(XRD), infrared spectroscopy(FTIR) and scanning electron microscopy(SEM). The results show that Praziquantel is crystalline in physical mixture, and amorphous in solid dispersions, which provides the basis for improving dissolution rate of drugs.Finally, this study established a determination method for praziquante content in plasma by a high performance liquid chromatography tandem mass spectrometry(HPLC/MS/MS). According to methodology experiments, the mentioned analysis methods are feasible with high specificity and good repeatability. Taking commercially available tablets as the reference, this essay studied the pharmacokinetic characters of praziquantel solid dispersions that applied to living dogs and analyzed the data of drug-plasma concentration by a pharmacokinetic software of DAS2. 1. 1 version to calculate pharmacokinetic parameters and relative bioavailability. The results proved the experiments in this essay help reduce Tmax of PZQ-SD dramatically, and increase Cmax of PZQ-SD and the area under the curve(AUC) significantly. Compared with the commercially available tablets, the relative bioavailability of PZQ-SD prepared through experiments mentioned in this essay reached up to 236.22%. The great changes strongly support the solid dispersion technology improves the bioavailability of praziquantel impressively.To sum up, solid dispersion of Praziquantel, showing a better bioavailability than that of commercially available tablets has been managed to prepare through this study.