Study On Pharmaceutical Preparation And Transdermal Permeation In Vitro Of Progesterone

Transdermal drug delivery system (TDDS) attraets more and more attention for itsadvantages.However, the transdermal permeation was limited by the skin barrier.Chemical,pharmaceutics and physical methods have been used for enhancing transdermal drugtransportation.Ethosomal system with good fluidity, deformability and high entrapmentefficiency can significantly enhance the permeability.In order to develop a newlytransdermal delivery system, this thesis focused its attantion on preparing ethosome loadingProgesterone and its cataplasm for transdermal delivery, the permeation property in vitroand the quality evaluation.1Study on the ethosome loadingProgesterone1.1Study on the preparation of ethosome loading ProgesteroneAccording to the results of the preformulation study, the method of ethanolaffluxing-high pressure homogenization technique was used to prepare ethosome loadedwith progesterone.The particle size, entrapment efficiency, amount of24h accumulationpermeation of Progesterone and stability were taken as criterions to evaluate the effects ofdifferent amounts of lipid material, cholesterol, ethanol and so on.And the L9(34)orthogonal test method was used.The optimal prescription was Progesterone:2.0mg·mL-1,egg lecithin:25mg·mL-1, cholesterol3mg·mL-1, ethanol:45%(v/v), Polysorbate-80:10mg·mL-1.With this optimal prescription, better quality ethosome can be prepared.1.2Quality evaluation researches on ethosome loading ProgesteroneThe properties of ethosomes loaded with Progesterone were studied in detail in orderto make sure the quality of it.The surface morphology of ethosome was observed bytransmission electron microscope; the particle size and Zeta potential of ethosome weredetermined by a nanometer laser particle size analyzer; the entrapment efficiency ofethosome was determined by reverse dialysis method with HPLC.The results indicated thatthe average particle size, Zeta potential and entrapment efficiency and so on which related to physical and chemical properties were stable.2Study on the ethosome loading Progesterone cataplasm2.1Study on the preparation procedure of ethosome loading Progesterone cataplasmA appropriate matrix was sereened out and the bigger influential factors of matrix werepreliminary determined through the preliminary test and single-factor experiment.The L9(34)orthogonal test method was used and tacking strength, cohesive strength, physicalproperties and the amount of cumulative penetration of Progesterone were used asevaluation indexes.The optimal prescription was ethosome loading Progesterone:30g,Viscomate NP-700:3.0g, Dihydroxy alumimun aminoacetate:0.25g, Glycerol:20g, PVPK-90:3.0g, Tartaric acid:0.1g, Caoline:1.5g, Ethyl para hydroxybenzoate:0.03g.With thisoptimal matrix prescription better quality cataplasm can be prepared.2.2Quality evaluation researches on ethosome loading Progesterone cataplasmOn the research of the quality standard, the average weight of matrix, the weightdifference and the shapping of cataplasm met pharmacopoeia of the People’s Republie ofChina of2010edition.By the adhesion experiment, the result showed that it can stick on the23th ball (weight16.50g), and cohesive strength time was not less than80s. By the releasetest in vitro, the amount of Progesterone from cataplasm reached up to (86.24±1.99)%in6hour.At last, the amount of24h accumulation permeation was obtained as(130.15±8.69)μg·cm-2. Meanwhile, through the human skin irritative tests, it can be initiallythought that ethosome loading Progesterone cataplasm had not stimulating and allergicreaction to human skin.