Sdudy On Drug Dosage Forms Of Thymopentin Microemulsions

Thymopentin is a shorter peptides, which is consists of32～36active fragments(Arg-Lys-Asp-Val-Tyr) of Thymopoietin. Thymopentin is mainly used to treat cancer, chronic hepatitis, autoimmune disorders diseases in clinical treatment, which has the same biological function and efficacy as thymopoietin. It can be enzymolysised by aminopeptidase and protease when it is injected to body. The half-life of thymopentin in plasma is only30s. Because of its frequent injection, that is daily muscle injection of thymopentin is1～2times, the clinical treatment of thymopentin has brought a great physical, psychological and economic burden to the patients.Microemulsions, also called Nanoemulsions, which is a transparent or translucent, low viscosity, isotropic and thermodynamically stable solution system, which is spontaneously formed with appropriate proportion of the aqueous phase, oil phase, surfactant and cosurfactant. As a new drug carrier, microemulsions can keep the stability of protein and peptide drugs and make the drug rapid and complete absorbtion, thereby it can strengthen the curative effect, reduce toxicity and improve the bioavailability for drugs.This paper mainly studied the prescription screening, identification, stability test, the quality evaluation of blank microemulsion and thymopentin microemulsions and the method of determination and the non-injection dosage forms of thymopentin microemulsions that water-in-oil microemulsion as a drug carrier, and thymopentin as a model drug were also reseached.The preparation of thymopentin microemulsions is made by Km titration, stirring and titrating until slight opacitas, then drawing the pseudoternary phase diagrams. The formulation regions and the maximum load of water being indicators of the prescription screening of microemulsion, by single-factor tests, different dosage forms for thymopentin microemulsion including thymopentin microemulsion1(lecithin, containing alcohol) and thymopentin microemulsion2(Span80and Tween80, excluding alcohol) were screened. Through the method of centrifugation, dyestuff, dilution and conductivity, the microemulsions and inspect the acid and alkali resistance, ionic strength, stability, thermal stability were identified. Through the Zeta sizer, the size and distribution of the microemulsion, refractoscope for refractive index, rotation-viscometer for viscocity were determined, and the physical and chemical properties of the blank microemulsion and Thymopentin microemulsion was studied; The methods for pretreatment of protein drugs microemulsion are as follows:extraction method, acid hydrolysis method, surfactant demulsification method and so on. Through the comparative study of liquid nitrogen frozen method, acid hydrolysis method, saturated sodium chloride demulsification method, mobile phase demulsification method, methanol dilution method, Triton X-100demulsification method, the content of thymopentin microemulsion was determined, and the method for content determination of thymopentin microemulsion was established.Hollow suppositories of thymopentin microemulsion was prepared by using water-soluble base for rectal drug administration. Through the re-match of the stromatics, the best stability of the hollow suppository prescription and its quality were selected and evaluated ultimately.The results showed that the optimal prescription of thymopentin microemulsion was①IPM:lecithin and dehydrated alcohol:water=4:5:1.②IPM:Span80-Tween80:water=4.6:4.5:0.9. Both TP5-ME are water-in-oil microemulsion by identification. The particle size and polydispersity coefficient of TP5-ME1are14.6nm and0.851,12.8nm and1.000for TP5-ME2are all determined by Zeta Sizer; By using the orthogonal text, the best pretreatment method for TP5-ME1was10%TritonX-100demulsification method, ultrasound5min, centrifuged5000rounds per minute for5min; Acid hydrolysis demulsification method was applied for TP5-ME2; HPLC was used to determine the average content of TP5-ME1and TP5-ME2, the content respctively was (94.8±2.9)%and (97.3±0.4)%; The best prescription of HTS was PEG1500:S40=7:3, and1%glycerol was added, its weight variation is (1.1810±0.0088)g.In summary, the result indicated that the best prescription for making thymopentin microemulsion(TP5-ME) has good stability, moderate particle size, HPLC method for the determination of thymopentin in microemulsion is accurate, sensitive, simple, specific and can be used to control the quality of thymopentin microemulsion. And the HTS is uniform, exquisite, and has moderate hardness.