| Estradiol benzoate (EB) is used for estrogen replacement therapy (ERT) for postmenopausal women. Parenteral administration of Estradiol Benzoate has been widely applied because first-pass hepatic metabolism is avoided. Intramuscular injection and Estradiol Benzoate gel are applied for ERT.The overall objective of this research project is to develop a device for trandermal delivery system (TDS) of estradiol benzoate at a controlled rate over a period of 7 days for the effective treatment of climacteric symptoms in post-menopausal women. TDS can also be called patch. TDS of estradiol benzoate is an adhesive diffusion type controlled TDS, be composed of back film adhesive film and protected film. For the successful development a series of systematic studies have been conducted. These studies can be divided into (l)physicochemical characterization of estradiol benzoate; (2) component and characterization of adhesive; (3)selection of chemical enhancer; (4)in vitro skin permeation studies; (5)evaluation of patches' quality.UV method is used to determine solubility of estradiol benzoate indifferent solvent. Ethyl acetate has been selected for solvent in Estradiol benzoate TDS.The function of adhesive is not only as an adhesive, but also as a carrier of drug in TDS. When adhesive PSA(pressure sensitive adhesives) and Edugit 100 is 3:2(g:g) in TDS, the patches have good quick stick and shear strength, and patches do not make any skin irritation in FSHA irritation experiment. Its permeation rate crossing EVA film is faster than drug in PSA system, when estradiol benzoate in PSA/Edugit 100 system.HPLC methods is used to determine estradiol benzoate in estradiol benzoate TDS and its skin permeation in vitro. The blank sample ingredient interfere the determination when using UV methods determine estradiol benzoate. HPLC methods has been proved to be more precision and truly than UV methods. Average recovery of EB in HPLC methods is 95.2%; the detection limit is 0.015 g, theoretical plates are 7000, the precision with in day and between day RSD is 0.81% (n=5) and 1.7% (n=5) .In vitro drug percutaneous permeation has been studied with Franz diffusion one cell apparatus. Temperature in cell apparatus is (32?.5)癈, speed of magnetic force is 120r/min The major factor to change the drug percutanous permeation in experiment in vitro include: the characterization of animal skin and receptor medium. PEG400 aqueous solution has been selected as receptor medium. The mucosity of receptormedium will be stronger when concentration of PEG400 aqueous solution is promoted. This study profiles that 30% PEG400 aqueous solution is a good receptor medium.The permeation studies show that the abdominal skin is more permeable than back skin of guinea pigs. The drug percutanous permeation of abdominal skin is as 2.67 times as back skin of guinea pig in vitro. When guinea pigs' skin is dealt with chemical enhancer, cumulated drug percutaneous amounts and permeation rate are evidently increased.Azone Azone-PG and Azone-PG-OA have been selected in chemical enhancer studies. The studies profile that Azone-PG show good effect in enhancing estradiol benzoate percutanous permeation rate in vitro. When the patches contain 6%Azone and 30%PG, the highest percutanous permeation rate was observed.The prescription was given according to the results of studies in vitro. Three batches of estradiol benzoate patches were prepared continuously. Quick stick ,shear strength, content of estradiol benzoate and areas of estradiol benzoate patches have been determined. The results are accorded with desire.Three months' stability of EB patches is also evaluated. Temperature was 40 2 , relative humidity was 75% 5% Little polymer cold flow around the patches has been observed at higher temperature. Except thisphenomenon, no changes of physicochemical characterization about patches are observed. When the patches are stored at room temperature, there is no change of patches observed.The studies of releasing in vitro showed that the releasing curve of estradiol...
|
PDF Full Text Request