Taking Pudilan Xiaoyan Oral Liquid as a demonstration, the effective delivery of quality markers in alcohol precipitation of Chinese medicine oral liquid preparations was studied. With the transfer rates of adenosine, corynoline, cichoric acid, baicalin, and wogonin as evaluation indexes, the effect of the density of concentrate before alcoholic precipitation, volume fraction of ethanol, stirring speed, temperature of concentrated solution, stirring time, alcohol concentration, alcohol precipitation time, alcoholic precipitation temperature, alcohol addition rate, and the pH of concentrate on the alcohol precipitation process was investigated by Plackett-Burman trial design, thus obtaining the key factors that influenced the alcohol precipitation process. The key factors were further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. When the density of concentrate before alcoholic precipitation was 1.12 g·mL~(-1), the pH of concentrate was 6.86, and the alcohol concentration was 50.00%, the transfer rates of baicalin and wogonin were 91.86% and 87.78%, respectively. When the density of concentrate before alcoholic precipitation was 1.13 g·mL~(-1), the concentration of alcohol was 74.50%, and the alcoholic precipitation temperature was 17.0 ℃, the transfer rates of adenosine, corynoline, and cichoric acid were 85.95%, 71.62% and 83.19%, respectively. The method of optimizing alcohol precipitation techniques and determining the parameters of Pudilan Xiaoyan Oral Liquid by response surface methodology is reasonable and feasible, which provides guidance and experience for the effective delivery of quality markers in Chinese medicine oral liquid preparations.
Drugs, Chinese Herbal ; Ethanol ; Adenosine ; Chemical Precipitation

The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections, including concentrate density, concentrate temperature, ethanol content, flow rate and stir rate in the addition of ethanol, precipitation time, and precipitation temperature. Under the experimental and simulated production conditions, a series of precipitated resultants were prepared by changing these variables one by one, and then examined by HPLC fingerprint analyses. Different from the traditional evaluation model based on single or a few constituents, the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis (PCA) to comprehensively assess the performance of ethanol precipitation. Our results showed that concentrate density, ethanol content, and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants. The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products.
Chemical Precipitation ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; chemistry ; Ethanol ; Injections ; Principal Component Analysis

The theoretical basis of the alcohol precipitation process control was provided, the alcohol precipitation was optimized and the relationship equation was got. The monod glycoside, loganin and paeoniflorin were used as the evaluation indexes to determine the impact factors of alcohol precipitation techniques of Liuwei Dihuang decoction by the Plackett-Burman experimental design and the levels of non-significant factors were identified. Then, Box-Behnken response surface methodology was used to research and discuss the critical process parameters influence the effect of alcohol precipitation and draw interaction between key process parameters and the correlation equation with index components. Through the establishment and solving the quadratic regression model of composite score, the optimum preparation conditions of alcohol precipitation techniques of liuwei were as follows: stirring speed was 580 r x min(-1), standing time was 17 hours, alcohol concentration was 34%, the density of Liuwei Dihuang decoction was 1.13. The response surface methodology for optimized alcohol precipitation techniques of Liuwei Dihuang decoction is. reasonable and feasible.
Chemical Precipitation ; Chemistry, Pharmaceutical ; methods ; Drugs, Chinese Herbal ; chemistry ; Ethanol ; chemistry

Astragalus polysaccharide has been widely used in food and medicinal industry owing to its health-promoting properties. In order to characterize better the relationship among molecular weight, structure-activity and activities, a simple method was used different concentration of ethanol including 30% (PW30), 50% (PW50), 70% (PW70), 75% (PW75), 80% (PW80) and 90% (PW90) to precipitate Astragalus polysaccharides into different molecular weight. As a result, PW90 showed smooth surface and the strongest antioxidant activity among these six fractions (P < 0.05). In conclusion, graded ethanol precipitation was a simple method to separate Astragalus polysaccharides into different molecular weight with different antioxidant activity fractions.
Antioxidants ; pharmacology ; Astragalus Plant ; chemistry ; Chemical Precipitation ; Ethanol ; chemistry ; Polysaccharides ; chemistry ; pharmacology

A set of central composite design experiments were designed by using four factors which were ethanol amount, ethanol concentration, refrigeration temperature and refrigeration time. The relation between these factors with the target variables of the retention rate of schizandrol A, the soluble solids content, the removal rate of fructose and the removal rate of glucose were analyzed with Bayesian networks, and ethanol amount and ethanol concentration were found as the critical process parameters. Then a network model was built with 2 inputs and 4 outputs using back propagation artificial neural networks which was optimized by genetic algorithms. The R2 and MSE from the training set were 0.983 8 and 0.001 1. The R2 and MSE from the test set were 0.975 9 and 0.001 8. The results showed that network analysis method could be used for modeling of Schisandrae Chinensis Fructus ethanol precipitation process and identify critical operating parameters.
Bayes Theorem ; Chemical Precipitation ; Cold Temperature ; Cyclooctanes ; chemistry ; Ethanol ; chemistry ; Fructose ; analysis ; Fruit ; chemistry ; Glucose ; analysis ; Lignans ; chemistry ; Neural Networks (Computer) ; Polycyclic Compounds ; chemistry ; Reproducibility of Results ; Schisandra ; chemistry ; Time Factors

Near infrared (NIR) spectroscopy as a kind of rapid process analysis technology has been successfully applied in Chinese medicine pharmaceutical process. In this research, the technology was adopted to establish the rapid quantitative analysis models of main indicators from the Lonicera japonica and Artemisia annua alcohol precipitation process of Reduning injection. On-line NIR spectra of 142 samples from alcohol precipitation process were collected and the content of main indicators for each sample were detected through off-line HPLC. With eliminating outliers, determination of spectra pretreatment method and selecting optimal band, the NIR quantitative calibration model for each indicator was established using partial least squares (PLS). These models were used to predict the unknown samples from precipitation process of Reduning injection to achieve the goal of rapid detection. The results showed that the models were ideal. The correlation coefficients of models for neochlorogenic acid, chlorogenic acid, 4-O-caffeoylquinic acid and secoxyloganin were 0.973 872, 0.985 449, 0.975 509 and 0.979 790, respectively and their relative standard errors of prediction (RSEP) were 2.922 49%, 2.341 37%, 2.930 40% and 2.184 60%, respectively. This study indicated that the NIR quantitative calibration model showed good stability and precision, and it can be used in rapid quantitative detection of main indicators of efficacy in order to on-line monitor the alcohol precipitation process of Reduning injection.
Chemical Precipitation ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Ethanol ; chemistry ; Lonicera ; chemistry ; Quality Control ; Spectroscopy, Near-Infrared ; methods

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.
Acetone ; chemistry ; Antineoplastic Agents ; chemistry ; pharmacokinetics ; Chromatography, High Pressure Liquid ; Drug Compounding ; methods ; Ethanol ; chemistry ; Fractional Precipitation ; methods ; Lactic Acid ; chemistry ; Microscopy, Electron, Scanning ; Nanoparticles ; chemistry ; ultrastructure ; Nanotechnology ; methods ; Particle Size ; Polyethylene Glycols ; chemistry ; Polyglycolic Acid ; chemistry ; Succinates ; chemistry ; Surface Properties ; Taxoids ; chemistry ; pharmacokinetics

OBJECTIVETo suggest a method for discriminating quality control indicators of concentrated solution before traditional Chinese medicine ethanol precipitation.

METHODThe second ethanol precipitation (SEP) of Guanxinning was taken as an example, with the concentrated supernatant of first ethanol precipitation (CSFEP) prepared with same dry matter content and the same amount of ethanol as raw materials, to conduct the ethanol precipitation test under the same conditions. The experimental data was analyzed by stepwise regression and partial least squares regression. Both of them selected the parameters which affect phenolic compounds retention ratios in SEP supernatant as the key indicators.

RESULTPhenolic compounds contents in SEP supernatant were mainly affected by the contents of danshensu, caffeic acid and salvianolic acid B in CSFEP.

CONCLUSIONThe discrimination method can be used to discover key quality control indicators of concentrated solution before ethanol precipitation.

The method of near infrared spectroscopy was established to analyze the content and transfer rate of the marker component, indole alkaloids, of cinobufacini in the process of ethanol precipitation. The samples of cinobufacini were collected, and the concentration of indole alkaloids was determined by the reference method, UV-vis spectroscopy. After the rejection of abnormal samples, the pretreatment of spectra and the choice of the corresponding wave band, the multivariate calibration models were established using PLS algorithm between spectra and the UV values. The samples in ethanol precipitation, which did not participate in modeling, were used to examine the performance of the models. The correlation coefficient of the calibration model was 0.9613. Root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were 0.172 and 0.169, respectively. Furthermore, residual predictive deviation (RPD) of the model was 4.13, which meant quantity analysis was feasible. It is concluded that near infrared spectroscopy can be considered as a fast, effective and non-destructive analysis method applied in the process of ethanol precipitation for traditional Chinese medicine.
Algorithms ; Bufanolides ; chemistry ; Calibration ; Chemical Precipitation ; Ethanol ; chemistry ; Indole Alkaloids ; analysis ; metabolism ; Least-Squares Analysis ; Multivariate Analysis ; Spectroscopy, Near-Infrared ; methods

OBJECTIVETo investigate the optimal alcohol precipitation parameters for extract of Carthamus tinctorius.

METHODSThe effects of different factors on the transfer rate of hydroxy safflower yellow A (HSYA) was studied via single factor experiments, including the final alcohol concentration of the liquor, the speed of stirring, the initial density of the extract, the temperature and the pH of the liquor. Based on the results of single factor experiments, the final alcohol concentration of the liquor, the speed of stirring, the initial density of the extract and the pH of the liquor were studied by an orthogonal test and a multiple guidelines grading method, and the transfer rate of HSYA, the yield and the purity of extract in the supernatant were used as comprehensive evaluation index.

RESULTThe optimal alcohol precipitation process of Carthamus tinctorius extract was as follows: the final alcohol concentration of the liquor 50%, the speed of stirring 500 r/min, the initial density of the extract 1.15 g/ml and the pH of the liquor 5.0.

CONCLUSIONThe proposed alcohol precipitation process is convenient and steady with high transfer rate of HSYA, high yield and purity of extract in the supernatant.