Study On Preparation And Quantitative And Qualitative Methods Of Shuxiong Tablets

Sublingual administration belongs to non-invasive administration withthe features of convenience, no first pass effect, fast absorption and highbioavailability, etc. It has been widely used in cardiovascular medicine andmany other drugs.The first sublingual drug is for treatment of angina pectoris. Theadvantages of sublingual administration are mainly:1.The sublingual mucosa has good permeability and short path forosmosis. With abundant blood vessels under the tongue, the drugs candirectly enter the systemic circulation through the capillaries, so they canbe rapidly absorbed and have positive effects. Sublingual medication canbe administered systemically;2. Sublingual administration can avoid the first pass effect of liver andgastrointestinal damage and degradation. It helps maintain the efficacy andimprove the bioavailability of drugs, but also can reduce their toxic andside effects on gastrointestinal and liver.3. The sublingual route of administration is simple and has bettercompliance.4. Compared with the nasal mucosa, tongue mucosa is not easy to bedamaged with strong repair function, or cause mucosal damage, so it ismore safe.Shuxiong tablet consists of Chuangxiong、Safflower and Sanqi. It ismainly used in the treatment of coronary heart disease, angina pectoris andarrhythmia. The ginsenoside Rg1in Sanqi and ferulic acid (FA) in Chuanxiong have good transmucosal foundation in vitro. According to thecharacteristics of Shuxiong prescription, we modified it into sublingualadministration. It aimed to provide a new preparation with convenience,fast effects, high bioavailability and good stability for the clinical.Part I Optimization of extraction process of Chuanxiong andSafflowerThe contents of FA in chuanxiong and HSYA A in Safflowerweredetermined by high performance liquid chromatography(HPLC). Thestandard curve equation of FA was Y=95785X+58479, R2=0.998. Itshowed that there was a good linear relationship between the concentrationof FA in the concentration range of1.7~10.2μ g/ml. The standard curveequation of HSYA A was Y=16842X-10835，R2=0.998. It showed that therewas a good linear relationship between the concentration of HSYA A in theconcentration range of3.6~21.6μ g/ml.Ultrasound extraction of Chuanxiong, Safflower with ethanol: basedon the Orthogonal test, the transferring rates of HSYA and FA wereregarded as the index to evaluate extracting conditions such as the ethanolconcentration, ratio of solid to liquid, extracting duration and extractingtimes. The optimum extract conditions of FA and HSYA are: with12timesvolume of ethanol with50percent of concentration as the extract liquid, toextract two times,20minutes every time.Part II Optimization of Shuxiong tablets molding processThe synthetic weighted mark method is to determine the weight of theresults of multi-index by the importance of each index during the test. Thetest results of multiple indicators transform into the test results of singleindex. Then according to the single index analysis method to comprehensive optimization of the scheme. This experiment studied thatthe effects of Lactose and mannitol ratio, dosage, microcrystalline cellulosecontent on the granulation. Based on the Orthogonal test，the appearance,hardness, and friability of the tablet were regarded as the index to evaluateextracting conditions. The best molding materials are：the ratio of herbalextracts tolactose and mannitol is1/9and the ratio of herbal extracts tolactose and mannitol to microcrystalline cellulose is6/8/0.5.According tothis formula, the samples have good quality and repeatability.Part III Optimization of Processing Technology and ComplexAccelerators of Shuxiong Sublingual TabletAzone, oleic acid, menthol is commonly used in skin and mucosadelivery enhancers. The Sublingual tablets were made by lactose, mannitoland MCC using orthogonal test. According to central compositedesign-response surface methodology, drug vitro permeation tests wereperformed in Frank diffusion cell. The accumulation transmittance ofGinsenoside Rg1concentration in samples was determined by HPLC. TheShuxiong sublingual tablet was made by dry extract powders, lactose andmannitol (the ratio of dry extract powers to lactose and mannitol is1/9)andMCC (the ratio of the three is6/8/0.5).The best complex accelerators werecomposed of2percent of Azone,2percent of Oleic acid and5percent ofmenthol. Considering the cost and so on, finally we chose6percent ofazone or6percent of oleic acid alone as the penetration enhancer.Part IV Establishment of Shuxiong tabletsQuantitative and qualitative methods1. To establish the qualitative analysis of TLC method for the ferulic acidand ginsenoside Rg1in Shuxiong tablets. 2. To establish HPLC method for quantitative detection of ginsenosideRg1、Rb1andNotoginsenoside R1.