Near-infrared Spectroscopic Quality Control on Coating Process of Vitamin C Yinqiao Tablets / 中国实验方剂学杂志

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（Rp2） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Analysis of Safe Storage Moisture Content of Mume Flos Decoction Pieces Based on Theory of Water Activity and Water Molecular Mobility / 中国实验方剂学杂志

ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic［water activity（Aw）］ and microscopic（water molecular mobility）， which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method， and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient（R2） was closer to 1， residual sum of squares（RSS） was closer to 0 and Akaike information criterion（AIC） was smaller. According to the optimal model， the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ was calculated. Low-field nuclear magnetic resonance（LF-NMR） was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression， the absolute safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ were 9.59%， 7.96% and 7.68%， and the relative safe moisture contents were 13.05%， 11.99%， 11.77%， respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures， namely bound water T21 and free water T22. During the process of hygroscopic absorption， bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents， and the R2 were 0.959 9， 0.911 8 and 0.974 7 at 25， 35， 45 ℃， respectively. When Aw<0.57， T21 did not change， and the water molecular mobility remained unchanged. When Aw>0.57， T21 showed an increasing trend， and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%， 6.81% and 6.25% when the water molecular mobility increased at 25， 35， 45 ℃， respectively. ConclusionCombined with the theory of water activity and water molecular mobility， 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces， this study can provide reference for determining the safe storage moisture content of other decoction pieces.

Scientific Characterization of Traditional Softening Method of Corydalis Rhizoma / 中国实验方剂学杂志

ObjectiveModern scientific methods and techniques were used to scientifically characterize the traditional softening process of Corydalis Rhizoma， so as to clarify the scientificity and rationality of the traditional process， and provide reference for inheriting the processing methods and experience of traditional Chinese medicine. MethodLow-field nuclear magnetic resonance imaging （LF-NMR/MRI） was used to characterize the water types and distribution in the softening process of Corydalis Rhizoma. Samples during the softening process was cut into thick slices and its section was observed by stereoscopic microscope. High performance liquid chromatography （HPLC） was employed to determine the content change of tetrahydropalmatine during the softening process with the mobile phase of methanol-0.1% phosphoric acid solution （60∶40， triethylamine regulated to pH 6.5） and detection wavelength at 280 nm. The determination method of softening endpoint of Corydalis Rhizoma was simulated by texture analyzer （hand pinch method）， and the softening degree of the finished products was determined after optimizing the relevant parameters. ResultLF-NMR/MRI showed that the water could penetrate through the core and distribute evenly in Corydalis Rhizoma softened by Zhangbang method. The water first entered into the medicinal material from the epidermis and stem marks in the soaking stage as the form of free water， and then penetrated into the inner core to achieve redistribution in the moistening stage. Under stereoscopic microscope， it was observed that Corydalis Rhizoma softened by the Zhangbang method could be sliced well， but the core bursting slices were easy to appear if the softening time was not enough， and the softening of samples was caused by the keratine-like powder after absorbing water. HPLC measurement showed that the loss of tetrahydropalmatine in the softening method was small， its content decreased about 5% in the soaking process， and its content was almost unchanged during the moistening process. The softening degree of Corydalis Rhizoma could be quantified by the texture analyzer， and the optimum parameters were 2 mm·s-1 of speed before test， test speed and speed after test， 20 g of the trigger force， 20% of compression degree. The compressive force of the qualified softened Corydalis Rhizoma was 12.75-15.69 N with the relative standard deviation （RSD） of 6.8%. ConclusionModern scientific methods and techniques can characterize the scientificity and rationality of the traditional processing methods， and confirm that the Zhangbang softening method has the advantages of high efficiency， convenience and small loss of index components. The texture analyzer can simulate the softening endpoint judgment method （hand pinch method）， and realize the goal from subjective experience judgment to objective technology quantification， which has a good demonstration role for the modern inheritance of traditional processing technology.

Scientific Characterization of Traditional Softening Method of Corydalis Rhizoma / 中国实验方剂学杂志

ObjectiveModern scientific methods and techniques were used to scientifically characterize the traditional softening process of Corydalis Rhizoma， so as to clarify the scientificity and rationality of the traditional process， and provide reference for inheriting the processing methods and experience of traditional Chinese medicine. MethodLow-field nuclear magnetic resonance imaging （LF-NMR/MRI） was used to characterize the water types and distribution in the softening process of Corydalis Rhizoma. Samples during the softening process was cut into thick slices and its section was observed by stereoscopic microscope. High performance liquid chromatography （HPLC） was employed to determine the content change of tetrahydropalmatine during the softening process with the mobile phase of methanol-0.1% phosphoric acid solution （60∶40， triethylamine regulated to pH 6.5） and detection wavelength at 280 nm. The determination method of softening endpoint of Corydalis Rhizoma was simulated by texture analyzer （hand pinch method）， and the softening degree of the finished products was determined after optimizing the relevant parameters. ResultLF-NMR/MRI showed that the water could penetrate through the core and distribute evenly in Corydalis Rhizoma softened by Zhangbang method. The water first entered into the medicinal material from the epidermis and stem marks in the soaking stage as the form of free water， and then penetrated into the inner core to achieve redistribution in the moistening stage. Under stereoscopic microscope， it was observed that Corydalis Rhizoma softened by the Zhangbang method could be sliced well， but the core bursting slices were easy to appear if the softening time was not enough， and the softening of samples was caused by the keratine-like powder after absorbing water. HPLC measurement showed that the loss of tetrahydropalmatine in the softening method was small， its content decreased about 5% in the soaking process， and its content was almost unchanged during the moistening process. The softening degree of Corydalis Rhizoma could be quantified by the texture analyzer， and the optimum parameters were 2 mm·s-1 of speed before test， test speed and speed after test， 20 g of the trigger force， 20% of compression degree. The compressive force of the qualified softened Corydalis Rhizoma was 12.75-15.69 N with the relative standard deviation （RSD） of 6.8%. ConclusionModern scientific methods and techniques can characterize the scientificity and rationality of the traditional processing methods， and confirm that the Zhangbang softening method has the advantages of high efficiency， convenience and small loss of index components. The texture analyzer can simulate the softening endpoint judgment method （hand pinch method）， and realize the goal from subjective experience judgment to objective technology quantification， which has a good demonstration role for the modern inheritance of traditional processing technology.

Determination of Related Indexes in the Concentration Process of Huagai San Extraction Solution by Online Collection Technology for Near Infrared Spectroscopy / 中国药房

OBJECTIVE：To establish the method for online rapid detection of related indexes in the concentration process of Huagai san extraction solution ，and to provide reference for judgment of concentration end point. METHODS ：Online diagram of 73 concentrated samples in the concentration process of Huagai san extraction solution were drawn by NIRS online collection equipment. The partial least squares （PLS）method was used to establish the NIRS quantitative calibration model of 5 related indexes （concentration density ， solid content ， the contents of amygdalin ， ephedrine hydrochloride and pseudoephedrine hydrochloride）. Another 15 samples were used to validate the model ，and the correlation of predicted value and measured value was analyzed. RESULTS ：The correlation coefficients （R2）of the concentration density ，solid content ，the contents of amygdalin ， ephedrine hydrochloride and pseudoephedrine hydrochloride in the quantitative calibration model were 0.982 5，0.999 9，0.998 3， 0.999 4 and 0.999 3，respectively；the root mean square errors of calibration （RMSEC）were 0.001 6，0.025 1，0.014 7，0.001 8 and 0.000 9；the root mean square errors of cross validation （RMSECV）were 0.002 1，0.035 8，0.033 6，0.006 3 and 0.001 3， respectively. After validation by 15 samples，root mean square errors of prediction （RMSEP）were 0.003 2，0.024 6，0.021 5， 0.007 7 and 0.005 9，respectively. CONCLUSIONS ：The established quantitative calibration model has good predictability and can provide basis for online judgment of concentration end point of Huagai san extraction solution.

Study on Preparation of Paclitaxel-sorafenib-PLGA-loaded Embolic Microspheres and in vitro Drug Release Characteristics / 中国药房

OBJECTIVE： To prepare Paclitaxel-sorafenib-PLGA-loaded embolic microspheres， and to establish a method for the content determination and investigate their in vitro drug release characteristics. METHODS： Paclitaxel-sorafenib-PLGA-loaded embolic microspheres were prepared by emulsification-solvent evaporation method. HPLC method was used to determine the contents of paclitaxel and sorafenib in Paclitaxel-sorafenib-PLGA-loaded embolic microspheres； drug-loading amount and encapsulation efficiency were calculated. The determination was performed on Agilent TC-C18 column with mobile phase consisted of water-acetonitrile （40 ∶ 60，V/V） at the flow rate of 1.0 mL/min. The detection wavelength was set at 228 nm， and column temperature was 28 ℃. The sample size was 10 μL. The morphology of the microspheres was observed by optical microscopy and scanning electron microscopy. The particle size and granularity distribution of microspheres were measured by laser granularity analyzer. The release rates of paclitaxel and sorafenib were determined by HPLC under physiological temperature （37 ℃）. The reaction rate constants were predicted by Arrhenius equation at 37 ℃， and compared with the measured value （37 ℃）. RESULTS： The linear range of paclitaxel and sorafenib were 2.0-400.0 μg/mL （both r＝0.999 6）. The quantitative limits were 1.902 6 and 1.890 2 μg/mL， and detection limits were 0.985 5 and 1.264 5 μg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％. The recoveries were 99.00％-102.91％ （RSD＝1.12％， n＝9） and 98.39％-102.96％ （RSD＝1.94％， n＝9）. The surface of the microspheres were spherical， smooth and no protuberance and no adhesions. The average particle size was （139±1.16） μm. Drug-loading amounts of paclitaxel and sorafenib were 1.12％ and 0.85％， respectively. The encapsulation efficiency were 73.11％ and 58.65％， respectively. Accumulative release rates were （71.83±3.96）％ and （81.44±6.02）％ within 41 d at 37 ℃. RSDs for relative standard deviation of prediction reaction rate constant to measured value were less than 10％ for paclitaxel and sorafenib. The similarity factors were 83.53 and 73.95. CONCLUSIONS： Paclitaxel-sorafenib-PLGA-loaded embolic microspheres are successfully prepared. The microspheres have good morphology and sustained release. The predicted release curve is well correlated with the measured release curve. Established determination method is simple and stable.

Determination of Drug Loading and Encapsulation Efficiency of Epirubicin Hydrochloride-sorafenib PL-GA Embolic Microspheres by HPLC / 中国药房

OBJECTIVE:To establish a method for the determination of drug loading and encapsulation efficiency of Epirubi-cin hydrochloride-sorafenib-loaded Polylactic Acid-glycolic Acid Polymer(PLGA)embolic microspheres. METHODS:HPLC meth-od was adopted to determine the contents of epirubicin hydrochloride and sorafenib in the preparation,and then drug loading and encapsulation efficiency were calculated by formula. The determination was performed on Phenomenex Luna 5u C8(2) 100A col-umn with mobile phase consisted of methanol-water(containing 0.05% trifluoroacetic acid and 0.14% dium dodecyl sulfate)(75:25,V/V)at the flow rate of 1.0 mL/min. The detection wavelength was set at 252 nm,and the column temperature was maintained at 25℃. The injection volume was 10μL. RESULTS:The linear ranges were 2.020-101.00μg/mL for epirubicin hydrochloride(r=0.9998)and 2.048-102.40 μg/mL for sorafenib(r=0.9997),respectively. The limits of quantification were 3.2970,2.5468 μg/mL, respectively. The detection limits were 0.9891,0.7641 μg/mL,respectively. RSDs of precision,stability and repeatability tests were all less than 2.0%. The recoveries were 96.41%-101.80%(RSD=1.64%,n=9),99.46%-101.45%(RSD=0.70%,n=9),re-spectively. Drug loading of two components in 3 batches of samples were no lower than 1.17%,encapsulation efficiency no lower than 58%. CONCLUSIONS:The method is simple,accurate,can be used to determine drug loading and encapsulation efficiency of Epirubicin hydrochloride-sorafenib PLGA embolic microspheres.

Spray Drying Process of Anshen Bumian Granules / 医药导报

Objective To optimize spray drying process of Anshen bumian granules. Methods By using orthogonal design method, moisture content, powder rate and berberine hydrochloride content were indexes, and optimum technological conditions were determined. Results Proportion of microcrystalline cellulose, lactose and maltodextrin was 2??1??2. The extract was fed in at 6%. Optimum feeding in/out temperature for spray drying is 145 ℃ /85 ℃, liquid velocity was 30 mL??min-1 , and relative density of extract was 1. 15. Conclusion The process is reasonable and practical, has strong stability and good controllability, and it provides a basis for industrialized production.

Quality Analysis of Three Components in Shuanghuanglian Powder for Injection Before and After Ultrasonic Atomization / 医药导报

Objective To establish a new RP-HPLC method for simultaneous determination of chlorogenic acid,forsythin, and baicalin in shuanghuanglian powder for injection after ultrasonic atomization. Methods Hypersil ODS2 C18(250 mmí4. 6 mm,5 μm) was used as the chromatographic column. The mobile phase was methanol-0. 2% phosphate acid solution (4060). Flow rate was 1. 0 mL·min-1 . Sample volume was 5μL. Column temperature was 30℃. Detection wavelength was 324 nm at 0-10 min and 277 nm at 10-25 min. Results Contents of chlorogenic acid,forsythin, and baicalin had good linear relationship with the respective peak area (r≥0. 999 7) within the scope of the sample volume. The RSD was <2% for precision, reproducibility, and stability. Recovery rate was 98. 50%-101. 12% (n=6). Conclusion The method is rapid, accurate and reproducible, with high resolution. It can determine the content of three kinds of components at the same time. The three components in shuanghuanglian powder for injection did not change significantly before and after ultrasonic atomization.

A new water-soluble lubricant of tablets-L-leucine combined with PEG6000 / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare an effective and water-soluble lubricant.</p><p><b>METHOD</b>Co-sprayed lubricant (L-leucine and polyethylene glycol 6000 co-sprayed according to a certain proportion) and mixed lubricant (the physical mixture of spayed L-leucine and crushed polyethylene glycol 6000) were prepared and polyethylene glycol 6000, L-leucine, magnesium stearate, sodium stearyl fumarate and sodium chloride are crushed and sieved, respectively. Residual force, appearance of solution and disintegration time were considered as response variables of the lubrication effect to evaluate different lubricants. The changes of the co-sprayed lubricant were studied by differential scanning calorimetry, fourier infrared, electronic scanning microscope and X-ray diffraction.</p><p><b>RESULT</b>The efficacy of co-sprayed lubricant is better than other lubricants. Efficacy is improved by external form change without inner components and crystal changes.</p><p><b>CONCLUSION</b>Co-sprayed lubricant is a good water soluble tablet lubricant which has good efficacy.</p>

The mechanical properties and moisture permeability of eudragit L100/S100 free films affected by plasticizers and membrane materials ratio / 药学学报

The free membrane of Eudragit L100/S100 which is pH-sensitive, colon-specific was prepared by plane casting films. The film humidity, species and amount of plasticizers, the ratio of membrane material was investigated. The rate of membrane permeability and mechanical properties were used as indicators of orthogonal experiment, and its related properties were studied. The results show that the mechanical properties of the membrane and phragmoid capacity are the best when 30% TEC was used as plasticizer; the ratio of membrane material have little effect on the rate of membrane permeability and mechanical properties. By adjusting the species and amount of plasticizers, the ratio of Eudragit L100/S100, the free membrane which is colon-specific can be obtained.

Effect of alcohol concentration in water extraction and alcohol precipitation on preparation of effervescent tablets of Banlangen / 中国中药杂志

<p><b>OBJECTIVE</b>To study effect of alcohol concentration in water extraction and alcohol precipitation on the preparation of effervescent tablets of Banlangen.</p><p><b>METHOD</b>Effects of different concentrations of alcohol precipitation on the Banlangen extract rate, metastasis rate of index components, extract properties of powder, preparation process were investigated, respectively.</p><p><b>RESULT</b>Alcohol concentration on the Banlangen extract rate, metastasis rate of adenosine, extract the amount of saturated moisture, effervescent disintegration time of no significant impact, but spray drying process, dry granulation process.</p><p><b>CONCLUSION</b>Alcohol concentration has a significant effect on the preparation of effervescent tablets of Banlangen in the process of water extraction and alcohol precipitation, It suggest that the choice of concentration of alcohol precipitation should be based on experimental purposes, the entire preparation process of the system test results.</p>

Study on moisture sorption process model and application traditional Chinese medicine extract powder / 中国中药杂志

<p><b>OBJECTIVE</b>Study on the moisture sorption process characteristics of traditional Chinese medicine extract powder, to establish a mathematical model, provide a new method for in-depth study for moisture sorption behavior of traditional Chinese medicine extract powder and a reference for determine the production cycle, and predict product stability.</p><p><b>METHOD</b>Analyzed moisture absorption process of traditional Chinese medicine extract powder by utilized the law of conservation of mass and Fick's first law to establish the double exponential absorption model, fitted the moisture absorption data and compared with other commonly used five kinds of model to estimate the double-exponential absorption model.</p><p><b>RESULT</b>The statistical analysis showed that the coefficient of determination (R2) of double exponential model, Weibull distribution model and first order kinetics model were large, but the residues sum of squares (RSS) and AIC values were small. Synthesized the practical application meaning, we consided that the double exponential model was more suitable for simulating the process of Chinese medicine extract powder moisture absorption.</p><p><b>CONCLUSION</b>The double exponential is suitable for characterization the process of traditional Chinese medicine extract moisture absorption.</p>

Study on preparation of Qixian decoction pellets in tangential spray fluid bed / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare Qixian decoction pellets.</p><p><b>METHOD</b>The formulation and technological factors influencing the preparation of Qixian decoction were investigated in tangential spray fluid bed choosing the yield of pellets, particle diameter distribution, repose angle, bulk density as inspecting indexes.</p><p><b>RESULT</b>the technological parameters for the preparation of blank pellets were as follows: the ratio of starch and dextrin was 2:1, the adhesive agent was 70% syrup, the rotating speed was 200 r x min(-1), the air blow flow was 15 x 20 L x min(-1), the rate of air flow was 15 L x min(-1), the spay air pressure was 0.15 MPa, and the rotating rate of spray solution pump was 20-50 r x min(-1); The optimized technological parameters for the preparation of Qixian decoction were as follows: the relative density of the extract was 1.12-1.15 g x min(-1), the diluent was MCC and its quantity was 8%, the rotating rate of spray solution pump was 10-12 mL x min(-1), the frequency of the rotor disc was 18-20 Hz, the atomizing pressure was 0.2 MPa, the frequency of the fan was 22 Hz, and the spheronisation and drying time was 30 mins.</p><p><b>CONCLUSION</b>the appearance of the Qixian decoction pellets prepared in tangential spray fluid bed are smoothing and round, the yield of pellets are high, and pellets of the particle size between 500-700 microm is 90.6%.</p>

Experimental Study on Preparation Method for Xianglian Drop Pills (Rhizoma Coptidis and Radix Aucklandiae) / 中成药

The studies on the extract processes of Radix Aucklandiae and Rhizoma Coptidis, and the preparation method for Xianglian Drop Pills have been carried out. The preparation method included the adsorption of volatile oil of Radix Aucklandiae with the extract mixture of Radix Aucklandiae and Rhizoma Coptidis. Water in adequate amount was added into the above mixture, The mixture was grinded into homogeneous pasty, then added with melted PEG 4000. After being mixed well on water bath the mixed melt was poured into the home-made drop pill apparatus(at 90℃) preheated, dropped into dimethyl silicone at rate of 24 drops/min through the drop head with internal apeture for 45mm and external apeture for 6. 1mm、and cooled well. The drop pills were obtai ned by removal of dimethylsilicone. Every examination of prepared drop pills coincided with the requests in general notice of drop pills in Pharmacopoeia of the Republic of China(1990). The in vitro antibacterial test showed that Xianglian Drop Pills had the same antibiotic effect as Xianglian Pills did.

A Brief Account of the Study on Fufangdashen Tablets / 中成药

This article reviews the study on Compound Danshen Tablets. Based on collecting and analyzing literatures, about the pharmacological actions, preparation procedure, quality control methods, dosage improvement, etc. of Compound Danshen Tablets, it is considered that Compound Danshen Tablets has been extensively studied mrecent years, but quality control methods should be improved further and basic research should attract attention.