| Objective:In this study,microemulsion iodine was prepared,whose drug carrier was microemulsion,and we optimized its preparation technology,and evaluated its quality,antibacterial and safety of microemulsion iodine.Methods:(1)The appropriate Oil(Oil),surfactant(SF)and cosurfactant(CoSF)was selected via the pseudo-ternary phase diagram based on the chemical properties of the main drug.The optimal composition of Oil,SF,CoSF and water phase and preparation process were determined,for preparing O/W microemulsion iodine using the iodine.(2)Based on the Technical Standards For disinfection(Ministry of Health,2002 version),the physicochemical evaluation of microemulsion iodine included the appearance,pH,viscosity,density,particle size of microemulsion iodine were evaluated.And a determination method of iodine concentration in microemulsion iodine based on high performance liquid chromatography(HPLC)to establish and validate the methodology.Test pharmaceutical stability test was also carried out,including the storage conditions of time etc.(3)To study the antimicrobial activity of the microemulsion iodine against Staphylococcus aureus,Escherichia coli,Candida albicans and Pseudomonas aeruginosa,and to provide scientific basis for determining the effective concentration of iodine in microemulsion and its antibacterial effect.The further study of the microemulsion iodine resistance to drug-resistant bacteria was investigated via resistant bacteria test,and the tentative study of microemulsion iodine antibacterial mechanism was made.(4)The skin of rabbits as subjects,complete skin,damaged skin test and skin irritation test,were inspected and evaluated the safety of microemulsion iodine.Results:(1)The optimum composition of microemulsion iodine was obtained by the pseudo ternary phase diagrams,butyl acetate as Oil,Tween-80 as SF,and anhydrous ethanol as CoSF,and Km=1:1,SF/CoSF:Oil=8:2,SF/CoSF+Oil=55%,that was,the proportion is as follows butyl acetate was 11%,Tween-80 was about 22%,anhydrous ethanol was 22%,distilled water was about 44.5%,iodine was 0.5%(g/100 m L).The preparation process was as follows: Tween-80 and anhydrous ethanol were mixed evenly,then butyl acetate was added,then the main agent added,and finally the aqueous phase was added.Under the condition of 25℃,the stirring speed of 1300~2000 r/min was prepared by stirring up to 30 min.(2)The appearance of microemulsion iodine was wine red,clear and transparent liquid,the particle size distribution was between 10 ~100 nm and the average viscosity value was 35.8 mPa.s;the average density was 1.0095 g/cm3;and pH was 3.30~4.00.Determination of effective iodine in microemulsion iodine via HPLC: the linear range of I3-was 0.08~0.50 mg/m L,the RSD of intra-and inter-day were 0.5%~1.0% and 0.8%~1.3%,the recovery rate was between 97.2%~105.6%,the average recovery rate was 100.8%,and RSD was 3.1%.The effective iodine concentration of microemulsion iodine was 1.383 mg/m L~1.472 mg/mL,which was used two molecular iodine,RSD of each batch between 0.5%~1.0%.The results of stability test showed that the microemulsion iodine had good stability at low temperature test and accelerated test,except under the condition of high temperature,strong light levels were down a bit,both the appearance of each condition had no obvious change.(3)The minimum inhibitory concentration(MIC)of microemulsion iodine on Staphylococcus aureus,Pseudomonas aeruginosa was 0.012 mg/mL,Candida albicans and Escherichia coli was 0.023 mg/m L;the minimum bactericidal concentration of four kinds of bacterium(MBC)less than 0.094 mg/m L;effective iodine concentration between 0.012~0.090 mg/m L.Its bacteriostasis rate and bactericidal rate of the four kinds of bacterium were 100% within 2 min.The MIC and MBC of imidazoles drug resistance of Candida were 0.125 mg/mL.The results of biological membrane test showed that microemulsion iodine could effectively inhibit the growth of Candida albicans biofilm,so as to reach the role of sterilization and bacteriostasis.(4)The effective iodine concentration of 1.500 mg/mL on the rabbit’s complete skin,damaged skin and skin were no irritation.Conclusion:In this study,the microemulsion iodine was prepared successfully,and further investigated prescription screening,preparation technology,quality evaluation,antibacterial evaluation and safety evaluation.The pharmaceutics had the characteristics of increasing water solubility,covering iodine irritating odor,reducing iodine volatilization and so on.Its indicators were in full compliance with the Technical Standards For disinfection(Ministry of Health,2002 version),“2.1.1” the disinfectant kill microbial test,“2.3.3” the skin stimulation test and the 2015 version of Chinese Pharmacopoeia under the guidance of the principle of the stability test of raw materials and pharmaceutical preparations in the Fourth Edition.The utility model was a safe and highly effective external use antiseptic preparation,which had the advantages of low effective concentration of the effective iodine,short time of bacteriostasis and bactericidal,no stimulation of the skin and wide bactericidal spectrum.To provide a new formulation for external use iodine disinfectant and had certain practical application value. |
PDF Full Text Request