Study The Influence Rules Of Formulation Factors On Physical Stability Of Cream System With Span-tween As Compound Emulsifier

Chinese traditional drug cream belongs to one of the traditional formulations,as its features with less poisonous effect and easy to use and clean,this traditional formulations has been favored by the people increasingly.However,The results of undertaken survey of pharmaceutical showed that most cream existing different degrees of coalescence,creaming,water separation and other physical instability phenomena in the period of product validity.Physical stability is aways the bottleneck problem for Chinese traditional drug cream to development.The main factors which effected on physical stability of cream were formulation factors,preparation technology,storage conditions.But preparation technology may be most obvious.Throughout the domestic literatures on cream preparation research,it's easy to find that the great majority of study obtain stable cream preparation by change the types or content of cream base excipients.But it has been rarely reported that how would change in the types or content of cream base excipients impact the physical stability of cream.A representative cream preparation was composed of emulsifier and auxiliary emulsifier and water and oil and crude drug[2,3].The physical stability of creams are mainly determined by the gel network structure formed by those ingredients[4].This paper take gel network as point of penetration,more detailed researches are focused on how the emulsifier and auxiliary emulsifier and oil and chinese herbal monomer influence physical stability of cream by change the microstructure of cream.In addition,in order to facilitate correlation analysis between physical stability andmicrostructure of cream.Finding the cream microstructure information most relevant to the physical stability of cream.So thermogravimetric analysis and near infrared stability analysis technology were performed to quantitative characterization the physical stability of cream.The specific research ideas and conclusions are as follows:1.Effects of mixed ratios omixed emulsifier on microstructure and physical stability of cream systemIn this chapter,the total content of mixed emulsifier remained unchanged.Changing the mixed ratios of Span-60(S60)to Tween-80(T80).In the meantime,unchanging other ingredient.Four S60-T80 series and four S60-T60 series of creams were prepared respectively.Polarization microscopy?Thermogravimetric analysis?Conductivity measurements and Rheological examinations were performed to elucidate the systems' colloidal structure information.Additionally,Thermogravimetric analysis was carried out to quantitative characterization extent of the oil water dissociation of cream after subjected to different kinds of rigorous condition accelerated test.Near infrared stability analysis technology were performed to quantitative characterization the physical stability of cream.After that,extracting common factors from all the micstructure indicators of cream by factor analysis.Then,Investigating the relationship between common factors and physical stability of cream.The results showed that among the series of S60-T80 and S60-T60 creams with different mixed proportions,cream conductivity increase and more and more spherical lamellar liquid crystalline structures appear on micrographs with increasing span60 fraction,The greatest viscoelastic was appeared when the mass ratio of span and tween is 2:2.1:3 respectively,From thermogravimetric analysis the increase of span60 fraction led to the weight loss of the samples between 50-70? increase but decreasing within 70-110?.The results obtained for factor analysis and correlation analysis indicate that a positive correlation between the “intensity of the microstructure”,“ability of resistance to structural failure” of cream and physical stability of cream under most kinds of accelerated test,but “hydrophilic gel phase water content” has negative correlation to the physical stability.2.Effects of the types of oil on microstructure and physical stability of cream systemFive S60-T80 series and five S60-T60 series of creams were prepared with mixed emulsifier respectively,the mixed ratios of mixed emulsifier was fixed 2:2.Changing the types of oil,This chapter tries to give a explanations of how the types of oil affect microstructure and physical stability of cream system in term of the oil polarity,viscosity and alkyl chain length.The results show that among the series of S60-T80 and S60-T60 creams,the lower polarity the oil was and the nearer the oil alkyl chain length approximates to alkyl chain length of cetostearyl alchohol,then,the greater the storage modulus?loss modulus?the modulus value that equate the loss modulus and the storage modulus and yield value was;More viscoelastic structures with linear viscoelastic behaviour,The higher content of lipophilic gel phase water and the stronger physical stability and moisture retention capacity the cream was,in contrast.The larger is the difference between alkyl chain length of oil and cetostearyl alchohol or much higher polarity the oil was,the more disadvantageous gel structure formation in the cream,which makes cream poor physical stability and moisture retention capacity.3.Effect of mixed proportions of fatty alcohol on microstructure and physical stability of cream systemCreams were prepared with mixed emulsifier with the mixed proportions of Span-60(S60)to Tween-80(T80)was 2:2,the total content of fatty alcohol was fixed16%,while changing the mixed proportions of cetyl alcohol to stearyl alcohol.Using the method describing in the previous chapter to elucidate the systems colloidal structure information and quantitative characterization the physical stability of cream.The results show that creams prepared with mixing fatty alcohol were generally of a higher viscoelasticity,higher content of lipophilic gel phases water and better physical stability than those creams containing mono-fatty alcohol,However,among the mixing fatty alcohol creams,the mixed proportions of fatty alcohol markedly affects the results obtained from microscopic observation.The content of lipophilic gel phases water and viscoelasticity of cream,But no signally affects on the physical stability and humectant properties.4.Effect of the types of Chinese herbal monomer or microstructure and physical stability of cream systemChinese traditional drug creams were prepared with Flavonoids or Alkaloids Chinese herbal monomer.Using the method describing in the previous chapter to characterization microstructure and physical stability of cream.The results show that creams prepared with tetrahydropalmatine(protoberberinium tertiary amine alkaloids)or oxymatrine,matrine(both the two monomer are quiolizidine alkaloids)or naringenin(dihydroflavone)have a similar microstructure indicators to cream base and strong physical stability.However,There are significant differences in the microstructure indicators between cream base and baicalin(flavonoid glycosides)cream and baicalein(flavonoid aglycones)cream and berberine,palmatine(both the two monomer are protoberberinium quaternary amine alkaloids)cream.Furthermore,Comparing to cream base,cream containing baicalin or baicalein or berberine or palmatine has poorer physical stability.5.Explore the causes of the types of Chinese herbal monomer affect microstructure and physical stability of cream systemThis chapter analyzes the causes of the types of Chinese herbal monomer affect microstructure and physical stability of cream system from the physicochemical properties of Chinese herbal monomer,the effect of the types of Chinese herbal monomer on oil and water interface,the theory of solubility parameters and the interactions between Chinese herbal monomer and cream base material.The analysis shows that comparing to mother nucleus,substituents and electronic configuration of Chinese herbal monomer have greater influence on compatibility between Chinese herbal monomer and cream base material,In addition,The unstability of creams are caused by the following reasons: smaller oil-water participate coefficient of Chinese herbal monomer;greater surface tension,enthalpy-vaporization,hydrophilic surface area,hydrophobic portion,s longest chain length,molecular volumes and conductance of solution of Chinese herbal monomer;More lowering in the viscosity and penetrability of tween 80 solution by Chinese herbal monomer;Larger solubility parameters difference between Chinese herbal monomer and cream base material.