The Studies On Estradiol Liposome Nasal In Situ Gel

OBJECTIVE:To preparate and evaluate estradiol liposomes nasal in situ gel.METHOD:(1)The thin film dispersion method was used for preparing estradiol liposomes.(2)Ultraviolet spectrophotometry was determined scanning estradiol absorption wavelength and Sephadex gel selection to establish the method of entrapment efficiency of E2 determination.(3) The estradiol liposome entrapment efficiency and drug load were optimized as the index.(4)With microscope to observe the morphology of liposomes.(5) Characteristic of the viscosity of estradiol liposomes nasal in situ gel was studied, Regularity of the drug release was studied by using the Franz diffusion cell model and mechanism of the drug release was study by using the membrane—less dissolution model.(6) With the cumulative amount of estradiol in estradiol liposomes nasal in situ gel permeating mucosa in vitro as the index.(7) The preliminary stability of estradiol liposomes nasal in situ gel were investigated.(8) Using the HPLC method for the determination of estradiol liposome nasal in situ gel was studied in the determination of the content of estradiol.(9) The mucosa irritation experiments and cilia toxicity test of estradiol liposome nasal in situ gel.RESULTS:(1) The thin film dispersion method can prepare liposomes with high encapsulation efficiency.(2) Estradiol has a maximum absorption at 280nm, preferably G-50 liposomes eluted as estradiol gel column.(3) The optimum process of preparing estradiol liposomes were as follows:lecithin high potency:Cholesterol=5:1(W/W), lecithin high potency:E2=15:1(W/W), the encapsulation efficiency was 87.31%.(4) Observed by microscope, mostly unilamellar liposomes, particle size (106.4+65.8nm).(5) The viscosity tests of the gellan gum show that the viscosity of estradiol liposomes Nasal in situ gel employing 0.5% gellan gum as material was moderate, The process of endosmotic permeation of estradiol liposomes Nasal in situ gel in vitro across the mucosa followed one—order, The action of drug release of estradiol liposomes nasal in situ gel was diffusion and it was not erosion.(6) Best penetration enhancers was 20% of 1,2-propanediol glycol.(7) The results of preliminary stability experiments indicated that estradiol liposomes nasal in situ gel were stable and Stored at room temperature for one month content remained above 85%, in the short term can carry and use; and under refrigerated conditions showed no significant change.(8) HPLC assay method is simple, easy, effective measurement of estradiol liposomes in situ gel nasal quality.(9) Cilia toxicity and mucosal irritation test showed that estradiol liposomes in situ gel nasal cilia toxic side effects, almost no mucous membrane irritation.CONCLUSIONS:Liposomes reasonable estradiol nasal in situ gel preparation, reliable, quality control method is feasible;estradiol liposome nasal mucosa irritation situ gel is very small, ciliated non-toxic, is a new formulation for nasal administration of medicine, the lack of prevention and treatment of female menopause estrogen has a potential value, worthy of further research and development.