Study On Self-Microemulsifying Drug Delivery System Of Active Ingredients In Jiaotai Pill

Jiaotai Pill is composed of Coptis chinensis and Cinnamomum cassia,whose main ingredients is total alkaloid of Coptis chinensis and essential oil of Cinnamomum cassia respectively.Their poor solubility in water lead to be absorbed little by the gastrointestinal tract and low bioavailability.Self-microemulsifying drug delivery system(SMEDDS)is a novel drug delivery system.It has been used as a vehicle to improve the oral absorption of drug.So it is meaningful to develop self-microemulsifying drug delivery systems(SMEDDS)of active ingredients in Jiaotai Pill and its quality control method.1.The Extracting of Active Ingredients in Jiaotai Pill and Determination of ContentsObjective:To extract active ingredients from Jiaotai Pill and determine the total alkaloid and cinnamaldehyde contents in the extracts.Methods and Results:Coptis chinensis and Cinnamomum cassia were identified according to Chinese Pharmacopoeia.The total alkaloid and the essential oil were extracted from the medicinal materials by decoction and steam distillation respectively,with 7.2%and 1.79%extracting ratio.The detecting wavelength is 430nm for UV-vis.The linearity range was 5.38μg/ml～107.6μg/ml for berberine chloride(r=0.9998).The average content of the total alkaloid in the extraction was above 84%.Methyl salicylate was used as internal standard material in GC method. SE-54 fused-silica capillary column was used.The injector temperature was 220℃, and the detector temperature was 250℃.The temperature programming was 100℃～200℃with heating rate at 10℃/min.The linear ranges of cinnamaldehyde was 0.574 mg/ml～5.166mg/ml(r=0.9998),and the average content of cinnamaldehyde in cinnamon oil was above 86%.Conclusion:The quantity of medicine materials is stable,and the techniques of the extraction are reliable.The established quantitative methods are simple,accurate with good reproducibility and strong specificity;they can be used for the quality control of the extraction of Jiaotai Pill.2.Preparation of SMEDDS of Active Ingredients in Jiaotai PillObjective:To develop self-microemulsifying drug delivery system(SMEDDS) of active ingredients in Jiaotai Pill.Methods and Results:The solubility of the total alkaloid in different compositions was investigated by UV-vis.Cinnamon oil was selected as only oil phases based on the results of solubility.In the formulation of cinnamon oil,taking OP as the non-ionic surfactant and 1,2-propanediol as the co-surfactant can get the best effect of microemulsifying.Conclusion:The optimal self-microemulsion formula was composed of OP, 1,2-propanediol,cinnamon oil,and the total alkaloid from Rhizoma Coptidis with the ratio of 4:8:3:6.3.The Physicochemical Characteristics of SMEDDS of Active Ingredients in Jiaotai PillObjective:The quality evaluation of SMEDDS of active ingredients in Jiaotai Pill.Methods and Results:The solubility of the total alkaloid was investigated in microemulsion,compared with which in micellar solution.The basic physicochemical characteristics including the conductance,refraction rate,particle size and self-microemulsifying speed were studied.Berberine-loaded microemulsion's mean diameter was 15.8nm,which was smaller than blank one.The influencing factors in the gastrointestinal tract of dilution medium,diluting multiple and temperature on the degree of self-microemulsion were investigated.Preliminary stability test showed that the SMEDDS was stable at room temperature.Qualitative analyses of cinnamon oil were conducted by differential scanning calorimatry(DSC).From the spectrum of the graphs of DSC,it could be found that the stability of cinnamon oil was improved.Conclusion:SMEDDS could improve the solubility and the stability of the drug evidently.The environment of gastrointestinal tract had no influence on the SMEDDS. SMEDDS could be self-microemulsion efficiently and keep ME state in the gastrointestinal tract.4.Determination of the Effective Components in SMEDDS of Jiaotai Pill Active IngredientsObjective:To establish a HPLC method for the content determination of berberine chloride and cinnamaldehyde in self-microemulsifying drug delivery system(SMEDDS)of active ingredients in Jiaotai Pill. Methods and Results:HPLC method was used with C₁₈column and methyl cyanide-0.1M Sodium Dihydrogen Phosphate-0.025M SDS(56:22:22);the detecting wavelength is 265nm.The linear range was 2.6μg/ml～52μg/ml of berberine chloride(r=0.9997).The average content of berberine chloride in the formula was above 20%.The linear ranges of cinnamaldehyde was 3.4μg/ml～67.5μg/ml(r=0.9996),and the average content of cinnamaldehyde in the formula was above 10%.Conclusion:The determination method of berberine chloride and cinnamaldehyde in the preparation is accurate and reliable.It can be used for the quality control of SMEDDS of active ingredients in Jiaotai Pill.In conclusion,SMEDDS can promote the solubility of insoluble drugs.The acquired microemulsion with small particle size is stable.In short,the Jiaotai Pill prescription self-microemulsifying drug delivery systems(SMEDDS)is an effective way to promote the bioavailability and stability of the prescription.