The Study On Transdermal Penetration Of Different Soluble Zinc Salts

Pharmaceutic zinc salts have showed extensive pharmacological effects in clinical application,which had been in clinical treatment of anti-inflammatory, anti-ulcer, promote tissue repair, etc.The zinc conjugated linoleates (623, water-insolubility), zinc oxide(81, water-insolubility) and zinc gluconate (455,water-solubility) were selected as the modle of water-insolubility and water-solubility drugs in this subject. The effects of pH, dosage form and penetration enhancers on the penetration of zinc salts were studied.This thesis consists of four parts, percutaneous permeation properties of a water-insolubility zinc representative-zinc conjugated linoleates(ZCL) and ZnO were studied in the first part. UV method was set up to determine zinc salts, then the solibility of ZCL in different solvents and pH were investigated. It was shown that the solubility of ZCL was increasing with the decreases of PH,and increasing with the augment of temperature. Penetration experiment of ZCL results showed:the accumulative penetration amount (Q) of zinc conjugated linoleates was increasing with the augment of pH. The order of ZCL percutaneous permeation in different preparations was Carbomer gel> CMC-Na gel> W/O cream>Vaseline ointment.The significance order of the effect of penetration enhancers on the ZCL hydrogel was 3% oleic acid> 2% dimethylsulfoxide> 3% Azone> 5% Urea> 2% sodium glutamate,and the effects on the ZCL W/O cream was 3% Dimethylsulfoxide> 3% Oleic acid> 5% Urea> 3% Azone> 5% Sodium glutamate. The result of penetration experiment of ZnO was that ZnO showed poorly transdermal penetration, cannot penetrate the skin.In the second part,percutaneous permeation properties of a water-soluble zinc representative zinc gluconate was studied.It was shown that the accumulative penetration amount (Q) of zinc gluconate was increasing with the augment of pH. With the pH in the range of 5.0 to 7.0, zinc gluconate percutaneous penetration increased less obviously. The order of zinc gluconate percutaneous permeation in different preparations was Carbomer gel>CMC-Na gel>W/O cream>Vaseline ointment. The significance order of the effect of zinc gluconate penetration enhancers on the hydrogel was 2% sodium glutamate> 2% dimethylsulfoxide> 3% oleic acid> 3% Azone> 3% urea, and the effects on the zinc gluconate W/O cream was 3% dimethylsulfoxide> 3% oleic acid> 3% urea> 3% Azone> 2% sodium glutamate.The simulate of zinc salts released on the skin surface was studied in the third part. The result suggested:the accumulative penetration amount (Q) of zinc gluconate and ZCL in Carbopol or CMC-Na gel was higher than it released in the W/O cream or Vaseline ointment. Result of mathematic fitting models:zinc conjugated linoleates and zinc gluconate release process belong to Higuchi equation, relationship of cumulative release (Q) with time (t) can be described as Q=(?)According to the fitting results, Conjugated linoleic acid and zinc gluconate release process belong to Higuchi equation on the condition of solution with different pH, dosage forms with kinds of penetration enhancers.The maximum steady-state transdermal permeation rate of zinc gluconate and ZCL were 0.802 mg·cm-2·h-1/2 and 0.214.72 mg·cm-2·-1/2.In conclusion,the innovative study of different soluble zinc salts release and transdermal penetration behavior, can provide a theoretical basis and reference for the research medicinal penetration method and development of zinc formulations for transdermal administration.