A Study On TDD System Of Artesunate

As an anti-malaria, anti-schistosome, anti-parasite and anti-cancer drug,preparations of artesunate used in clinical are tablet, injection, suppository, liposome and so on. However ,artesunate eliminates rapidly from human's body, therefore, it is very necessary to study on it's transdermal delivery system for the low oral bioavailbility and short half-life. Objective: (1)To establish methods for study on the percutaneous penetration and determination of artesunate.(2)To determine octanol/water partition coefficient and study the relationship between octanollwater partition coefficients and transdermal speed constant. (3 )To select the reservoir vehicle and estimate the effect of pH,various proportion of IPAIwaterILPM and drug concentration upon percutaneous penetration.(4)To prepare EVAC membrane.(5)To prepare artesunate-TDD and study the quantity of artesunate TDD.(5)To prepare artesunate-TDD and study the quantity of artesunate TDD.(6)To study the releasing rule of Artesunate-TDD. Methods:(1)The best hydrolysis method is estimated by studying hydrolysis tempreture,alkaline concentration and hydrolysis time. Alkaline hydrolysis-UV analysis method is used for the determiantion of artesunate.(2)Improverd Franz-cell and hareless rat skin are used for the transdermal study of artesunate,and transdermal speed constant(J) is used for the estimation of receptor.(3)Octanol/water partition coefficient is determined by UV analysis method.Based upon the PH principle,the octanollwater partition coefficients are got and the relationship between octanollwater partition coefficients and transdermal speed constant is studied.(4)The dissolve solubility in various proportion of IPAlwater is determined by UV method. The supplement orthodox cross design is used for the selection of reservoir vehicle,transdermal speed constant(J) and accumulative amount of transdermal drug(Q) are used for the estimation of various reservoir vehicle.(5)Orthodox cross design is used for the estimation of preparation process of EVAC.(6)Dissolution ability and cling ability are used for the estimation of thicker.(7)Artesunate TDD which belongs to membrane-controll releasing type is prepared.Percutaneous penetration of artesunate TDD is studied by use of hareless skin and saline/alchol (7:3,V:V),the releasing rule is got by study on the transdermal profile of two types. Results:(1)The best hydrolysis method is 83 C,O. 1M NaoH and hydrolyzed by one hour,UV scanning chart suggests the detected wavelength is 238nm and the hydrolysate is steady in 12 hours.(2)The regression equations of saline, saline/alchol(7:3,V:V),distilled water,PH6.8 phosphate buffer are: Y=O.0044x + 0.0299, Y=0.0035K +0.0472, Y=0.0029x +0.0374, Y=0.0034x +0.0818 respectively, Higuchi equations are Q=99.34t-78.65, Q=103.51t+ 5.51, Q=97.47t-131, Q=79.8t-78.65 respectively, which suggest saline/alchol(7:3,V:V) is the best for the receptor.(3)Octanollwater partition coefficient is 24.64 and the relationship between octanollwater partition coefficients and transdermal speed contantsfollow a linear relationship. Whose equation is Y=0.12x+41,r=0.97.(4)The chart of dissolve solubility shows that dissolve solubility increases with increasing of WA proportion. But, dissolve solubility decreases in pure IPA.(5)The proportion of IPAlwater/IPM is 6:4:0.05,drug concentration is 1 SmgImI,pH is 4...