Study On Spray Of Hymecromone

Hymecromone has significant acaricidal activity, but because of poor water solubility, its clinical application was limited. With advantages of increasing solubility and transdermal absorption of drugs, microemulsion was mostly used for transdermal delivery. Spray could make drugs dispersed, reach the sites of action directly, absorb quickly and stability good. Based on taking advantages of microemulsion drug delivery and spray, hymecromone microemulsion spray was prepared in this study, and its quality, safety and efficacy was studied.1. Study before the prescription of hymecromone microemulsion. In order to determine oil-water partition coefficient of hymecromone and solubility in drug excipients, the maximum absorption wavelength was confirmed by UV spectrophotometry with the contrast solution of hymecromone, crude drug solution, blank microemulsion solution and hymecromone microemulsion solution to establish method of determing content of hymecromone by UV spectrophotometry. The results showed that the tested hymecromone sample solution had the maximum absorption in 324 nm but blank microemulsion solution had not. The calibration curve for the quantitative analysis of hymecromone by UV spectrophotometry was A=0.083x+0.0529(r=0.9986), the linear relationship was good in the range of 0μg/mL～30μg/mL and the average recovery was (100.26±2.83)%. The RSD of with-day and between-day precision were less than 1%, respectively. The oil-water partition coefficient of hymecromone was 15.67, Log P was 1.20. The solubility of hymecromone was small in oil phase, water or the pharmaceutical excipients. Its solubility in water was 0.16 mg/mL, in oil phase, such as ethyl oleate, GTCC, vitamin E Oil, IPM, was 1.40, 1.38, 1.25, 1.02 mg/mL, respectively, in sufactants, such as Tween80, Tween60, EL-35, RH40 was 27.55, 27.21, 21.33, 17.88 mg/mL, respectively, in cosufactants, such as Diethylene glycol monoethy ether, PEG400, 1,2-Propanediol and ethanol, were 44.65, 39.08 25.49 and 22.23 mg/mL, respectively.2. Studies of hymecromone microemulsion formulation and preparation technology. Through analysis of solubility of hymecromone in oil phases, sufactants and cosufactants, and drawing of pseudo-ternary phase diagram, microemulsion formation was determined and the effect of preparing microemulsion about the different order of adding hymecromone, dispersing ways and temperature on microemulsion preparation were investigated to determine microemulsion preparation technology. The results showed that the system of ethyl oleate/ RH40/n-butanol/azone/distilled water and the system of ethyl oleate/Tween80/ iso-prophl alcohol/azone/distilled water were easy to form microemulsion. The prescription with high drug content and good stable was 0.9% hymecromone, 22.5% Tween80, 22.5% iso-prophl alcohol, 5% ethyl oleate, 5% azone and 44.1% distilled water. The preparation technology was that adding hymecromone to the mixture of oil, surfactant, cosurfactant and azone, then ultrasounded 10 min, magnetic stirring in 40℃, until the drug completely dissolved, then dripped distilled water enough slowly to form microemulsion.3. Spray quality evaluation of hymecromone microemulsion. According to microemulsion prescription, 0.9% hymecromone microemulsion and its spray were prepared. The structure type of hymecromone microemulsion was judged by the method of centrifugation, staining and dilution. Its appearance and particle diameter distribution were investigated by transmission electron microscope and laser particle size analysator, respectively. The contents of hymecromone microemulsion were determined by UV spectrophotometry. The results showed that hymecromone microemulsion was the type of oil-in-water and the liquid was pallideflavens, clear, well-distributed with good flowability. pH was 6~7. The microemulsion drop presented spherical shape, and the drop size averaged 37 nm with a polydispersity index of 0.128, the particle size of 94% was range of 10～40 nm. The mean content of hymecromone was 8.54 mg/mL in the hymecromone microemulsion. The average filled volume of hymecromone microemulsion spray was 28.83 mL, the total times per bottle were 192, each volume per jet was 0.15 g, content of hymecromone each spray were 1.22 mg.4. Safety and efficacy evaluation of hymecromone microemulsion. Skin acute toxicity test, skin irritation test, in vitro and in vivo acaricidal experiment were used to evaluate the safety and efficacy of hymecromone microemulsion. The results showed that after administration of the test group of skin coating with 0.9% hymecromone microemulsion, rabbits in experiment period had no toxic reactions and death. 0.9% hymecromone microemulsion on the intact skin did not cause erythema and edema stimulation. On the broken skin, the irritant score was one after one hour, it belonged to mild stimulation, the irritant score was equal to or less than 0.5 after 24 hours, it was no irritant. The tested mites were all killed in vitro by 0.9% hymecromone microemulsion after 3 h, corrected mortality was 100% after 24 hours. Corrected mortalities were 7.14% and 60% of 0.9% hymecromone solution and 0.3 mg/mL dicofol solution group after 24 hours, respectively. Statistical analysis showed that the effect of killing mites of 0.9% hymecromone microemulsion was better than 0.3 mg/mL dicofol solution (P <0.01). The ears of tested rabbits were smooth and clean, with a little scars or no scar in ear canal by giving 0.9% hymecromone microemulsion in vivo at the 7th day, no live mites were found by microscopy, and at the 14th day, there was no scar in ear canal. The ears of tested rabbits which gave 0.3 mg/mL dicofol were clean, ear canal filled with scabs, a small amount of live mites were found at the 7th day, ant there was little scabs in the era canal at the 14th day. Score data showed that therapeutic effect of 0.9% hymecromone microemulsion was same as 0.3mg/mL dicofol(p>0.05).