| Objective: Capsaicin, the pungent extract of peppers, has many pharmacological effects, one of which is long-acting analgesic effect through act on nervous system with substance P in it. It can be used in many diseases, such as post-herpetic neuralgia, sciatica, neuralgia of diabetic patient and so on. It's a neurochemical and analgesia pharmacological tool drug, too, to study the process of sensory transmission with substance P. Widely interest and more study has been stirred. But the imitation and low solubility in water limit its clinical use.Cyclodextrin can form inclusion compound with many drugs. Through inclusion, the physicochemical properties, such as solubility, stability, the imitation, the smelly taste and so on, will be improved, so that the compliance of patient will be increased. Our study about capsaicin-β-cyclodextrin inclusion compound will provide us with a new analgesic drug with increased solubility and lowered imitation.Method: The solubility of capsaicin in distilled water with different pH value, in different organic solvents, in alcohol-water with different proportion was detected with HPLC method. The percutaneous experiment in vitro was made with the improved Franz diffusion cell as the diffusion device, the rat's different abdominal skin part were used as the permeation membrance, the solvent of PBS7.4:EtOH (50:50) as the receiving solvent at 36±1 degrees Celsius. The steady penetration rate, Js, and the lagged time, Tlag, will be get.With the same methods as above, changing the diffusion membrance to 0.45μm acetate fiber (oil), I tested the release rate in vitro of capsaicin and its inclusion compound. The Zero order, First order, Higuchi and Weibull curve fittings were done, too.Studied the interaction betweenβ-CD and capsaicin by changing the preparation method and factors of influence. The phase-solubility diagram was made through testing the solubility in different solvents at different degrees, and making the drug solubility as the ordinate and the concentration of cyclodextrin as the abscissa. The curve will tell us if the inclusion compound is formed and the equilibrium constant K through calculation. The imitation test of capsaicin to rabbits was made as follow: shave the wool about 5cm×5cm, then use 0.075% capsaicin and its inclusion compound as external application every day for 7 days and made a record of the skin conditions.Result: The solubility was dramatically increased when the pH value reached 9, although it didn't had significant difference before 9. The organic solvent and the increasing of alcohol could improve the capsaicin's solubility.The permeation rate of capsaicin in active full skin, skin with fat removed with scissor, skin with fat removed with organic solvents was 2.83μgcm-1·h-1, 7.88μgcm-1·h-1, 15.38μgcm-1·h-1 respectively.β-CD could increase the permeation rate in vitro of CAP , and this effect ofβ-CD has more influence on CAP compared with microemulsion ( prepared in this study) and sold ointment. With combination withβ-CD , the water- soluble transdermal enhancers, SDS or urea, could increase the Js of CAP to 132.73μg·cm-2·h-1, 1.89 times as high as the control.Under the test conditions, CAP and its inclusion compound released fast, with at least 79.17% released in 4h. The process of release was in accord with Weibull equation and the correlation coefficients, R, were all above 0.995.In a low concentration, theβ-CD and CAP will form inclusion compound and the molar ratio is 1:1 as the AN phase-solubility diagram shows. When the temperature was 25℃,36℃,45℃,β-CD has increased the solubility of CAP to 0.32 mg·mL-1,0.60 mg·mL-1,1.08 mg·mL-1 , respectively. So it was confirmed that the improvement of capsaicin's penetration rate is a result of increasing solubility by forming inclusion compound withβ-CD.Formed inclusion compound withβ-CD, the irritation of CAP to the healthy skin of rabbits decreases to some extent.Conclusions: CAP-β-CD inclusion compound prepared by co-kneading can increase the solubility and the penetration rate in vitro and lower the imitation. The data can be useful for the further study of CAP-β-CD inclusion compound for the transdermal drug delivery system.
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