Processing Magnoliae Officinalis Cortex with ginger juice: process optimization based on AHP-CRITIC weighting method and composition changes after processing / 中国中药杂志

The weight coefficients of appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol were determined by analytic hierarchy process(AHP), criteria importance though intercrieria correlation(CRITIC), and AHP-CRITIC weighting method, and the comprehensive scores were calculated. The effects of ginger juice dosage, moistening time, proces-sing temperature, and processing time on the quality of Magnoliae Officinalis Cortex(MOC) were investigated, and Box-Behnken design was employed to optimize the process parameters. To reveal the processing mechanism, MOC, ginger juice-processed Magnoliae Officinalis Cortex(GMOC), and water-processed Magnoliae Officinalis Cortex(WMOC) were compared. The results showed that the weight coefficients of the appearance traits, extract yield of standard decoction, and total content of honokiol and magnolol determined by AHP-CRITIC weighting method were 0.134, 0.287, and 0.579, respectively. The optimal processing parameters of GMOC were ginger juice dosage of 8%, moistening time of 120 min, and processing at 100 ℃ for 7 min. The content of syringoside and magnolflorine in MOC decreased after processing, and the content of honokiol and magnolol followed the trend of GMOC>MOC>WMOC, which suggested that the change in clinical efficacy of MOC after processing was associated with the changes of chemical composition. The optimized processing technology is stable and feasible and provides references for the modern production and processing of MOC.

Formulation optimization of emodin nanostructured lipid carriers by Box-Behnken response surface method and in vitro quality evaluation / 中国中药杂志

Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.

Preparation and in vitro quality evaluation of self-microemulsion co-loaded with tenuifolin and β-asarone / 中国中药杂志

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.

Extraction and purification of components from Bufonis Venenum / 中草药

Objective: To optimize the extraction and purification technology of liposoluble constituents from Bufonis Venenum. Methods: The total content of cinobufagin and resibufogenin was taken as the index, and the ethanol potency, solvent multiplication and extraction time were taken as the investigation factors. The optimum extraction process parameters was determined by orthogonal test. Through single factor investigation experiment combined with Box-Behnken response surface method, taking the expansion agent ratio, ratio of diameter to height, adsorbent and sample quantity as the investigation factors, the optimum purification process was selected and determined. Results: It was determined that the optimum extraction process for the addition was 10 times 85% ethanol for 90 minutes’ extraction, the best purification process for the expansion agent cyclohexane-chloroform- acetone was 4:3:3, column height and diameter was 7:1, adsorbent and sample volume was 5.5:1. The content of two kinds of toad poison base purified was up to 66.51%. Through the verification of three batches of amplification process, it was shown that the model fit well, and the separation and purification of toad poison ligand by silicone column chromatography had the advantages of simple operation, fast separation speed, and good separation effect. Conclusion: The selected process is reasonable and feasible, which provides technical reference and basis for the industrialization application of the product in the future.

Optimization of extraction process of Modified Yangyin Qingfei Decoction by Box-Behnken response surface methodology based on analytic hierarchy process / 中草药

Objective: To optimize the extraction process of Modified Yangyin Qingfei Decoction (MYQD). Methods: The effects of ethanol concentration, extraction time and extraction times on the optimization of extraction process of MYQD were investigated by multiple indicators comprehensive scoring and Box-Behnken response surface methodology. The content of verbascoside, chlorogenic acid, paeonol, and glycyrrhizic acid was simultaneously determined by HPLC, and the method of analytic hierarchy process was used to calculate the weight coefficient. Results: The optimum extraction process was as follow: using 69% ethanol for once extraction for 68 min. Conclusion: The optimum extraction process is simple and feasible, and the extraction efficiency of components is high, which can provide reference for the extraction process of MYQD.

Optimization of test solutions preparation of Panax notoginseng in Chinese Pharmacopoeia by Box-Behnken response surface methodology / 中草药

Objective: To study and optimize the preparation method of test solution from Panax notoginseng. Methods: The effects of extraction solvent, liquid-material ratio and extraction temperature on the optimization of the preparation method of test solution of notoginsenoside and ginsenosides in P. notoginseng were investigated by Box-Behnken response surface methology. The content of notoginsenoside R1, ginsenoside Rg1, and ginsenoside Rb1 was simultaneously determined by HPLC. Results: The optimum method was as follow: 75% methanol was used for once reflux extraction, the ratio of liquid-material ratio was 1:40, the extraction temperature was 100 ℃. Conclusion: The optimum preparation of test solution is simple and feasible, and the extraction rate of components is high, which provides a reference for the preparation of test solution from P. notoginseng.

Optimization of the Extraction Technology of Total Flavonoids from Combretum alfrdii / 中国药房

OBJECTIVE： To establish the method for content determination of total flavonoids from Combretum alfrdii， and to optimize the extraction technology of total flavonoids from C. alfrdii. METHODS： Using aluminium trichloride as， chromogenic agent， UV spectrum was adopted to determine the content of total flavonoids from C. alfrdii. Based on single factor test， ethanol volume fraction， material-liquid ratio， extraction time， extraction temperature and times were selected as investigation factors， and the content of total flavonoids was selected as response value， Plackett-Burman design was used to screen the factors that had significant influence on the content of total flavonoidsfrom C. alfrdii. Then steepest climbing test was adopted to confirm the optimum valuing range； the extraction technology of total flavonoids was optimized by Box-Behnken response methodology. RESULTS： The linear range of total flavonoids were 0.012-0.036 mg/mL （r＝0.999 9）； RSDs of precision， stability and repeatability tests were less than 3％； the recovery ranged from 92.98％ to 99.86％ （RSD＝2.71％， n＝6）. The optimal extraction technology included that 60％ ethanol， material-liquid ratio of 1 ∶ 34 （g/mL）， extracting for 3 times， lasting for 60 min， extraction temperature of 80 ℃. Under this technology， average content of total flavonoids from C. alfrdii was 2.71％ （RSD＝1.69％， n＝6）， and the relative error was 2.65％ compared with predicted value of the model （2.64％）. CONCLUSIONS： Established method is stable and reproducible， and can be used for content determination of total flavonoids from C. alfrdii. The optimized extraction method is stable and feasible.

Study on technology of dry granulation of Wenshen Zhuanggu Granule / 中草药

Objective: The optimum technological conditions of granule dry granulation of Wenshen Zhuanggu Granule (WZG) were optimized to improve production efficiency and ensure product quality and curative effect. Methods: The difficulty degree of granulation was studied by orthogonal test. The molding rate and the dissolved property of the granule determined the type and dosage of excipients for the evaluation index. Through single factor investigation test and combined with Box-behnken response surface method, the feed speed, rolling speed and rolling pressure were the independent variables, and the particle forming rate was dependent variable, in order to optimize process parameters of dry granulation. Results: The optimum proportion of excipients was the dextrin with 1:3 of the dosage of dry paste powder, 1:15 carboxymethy starch sodium, 1:90 of the micro-powder silica gel, the best granulation process for rolling wheel pressure 9.5 MPa, rolling speed 14.0 Hz, and feed speed 13.2 Hz. Through the amplification process validation of three batches, it showed that the WZG prepared by the optimized excipients and process parameters have the advantages of high molding rate, good melting and low moisture absorption rate. Conclusion: The selected process is reasonable and feasible, and it provides technical reference and basis for the industrial application of the product.

Optimization of processing technology of decoction pieces of Citri Reticulatae Pericarpium by Box-Behnken response surface methodology based on CRITIC-AHP weighted evaluation / 中草药

Objective To determine the weight coefficient and optimize the processing technology of decoction pieces of Citri Reticulatae Pericarpium (CRP). Methods The contents of narirutin, hesperidin, nobiletin, 3,5,6,7,8,3’,4’-heptamethoxy flavone (HF), and hesperetin were simultaneously determined by HPLC. The weight coefficient of each component was evaluated by CRITIC-AHP (analytic hierarchy process) methods. With composite score as index, Box-Behnken design-response surface methodology was adopted to investigate the effects of water addition, soaking time, and soaking temperature on the quality of the processed products and optimize the processing technology of decoction pieces of CRP. Results Optimal processing parameters were as follows: 33% of water was added to 1 000 g of herbs, soaking time was 64 min, and soaking temperature was 45 ℃. Conclusion The optimized processing technology is simple and feasible, which can provide a reference for the processing of decoction pieces of CRP. The method established to simultaneously determine the contents of five components in decoction pieces of CRP is rapid and reliable for controlling the quality of decoction pieces of CRP.

Preparation and quality evaluation of volatile oil from Acori Tatarinowii Rhizoma self-nanoemulsion / 中国中药杂志

In order to increase the solubility of volatile oil from Acori Tatarinowii Rhizoma, this study was to prepare self-nanoemulsion of volatile oil from Acori Tatarinowii Rhizoma . The prescriptions were preliminarily screened by miscibility studies, excipient compatibility tests, and pseudo-ternary phase diagrams, and then the optimal formulation was obtained by using the Box-Behnken response surface method, with particle size and drug-loading rate as the indicators. The self-nanoemulsion prepared by optimal prescription was characterized and evaluated for dissolution. The results showed that the optimal prescription for this volatile oil self-nanoemulsion was as follows: 41.7% volatile oil, 46.8% Tween-80, and 11.5% PEG-400. The prepared self-nanoemulsion was clear and transparent, with drug-loading of (192.77±1.64) mg·g⁻¹, particle diameter of (53.20±0.94) nm, polydispersity index of 0.230± 0.013, and Zeta potential of (-12.2±0.7) mV. The dissolution of self-nanoemulsion was higher than that of volatile oil. In this research, volatile oil served as the oil phase in self-nanoemulsion, so the prescription was simpler and the drug loading rate was higher. The prepared self-nanoemulsion complied with the relevant quality requirements, providing a reference for the preparation of volatile oil formulations.

Optimization of Extraction Process for Walnut Quinone from Juglans Green Peel by Box-Behnken Response Surface / 中国中医药信息杂志

Objective To optimize extraction process of walnut quinone from Juglans green peel. Methods On the basis of single factor tests, taking material-liquid ratio, extracting temperature and ethanol concentration as independent variables, yield of walnut quinone in response to as a value, according to Box-Behnken experiment design principle, extraction process of walnut quinone from Juglans green peel was optimized by response surface analysis. Results The optimum extraction process of walnut quinone was: 14.30 times the amount of 89.81% ethanol;30.28 ℃ constant temperature. The extracting amount of walnut quinone was 2.034 mg/g, which was close to the experimental results of 1.957 mg/g. Conclusion The optimized extraction process is reasonable and feasible, which can provide reference for the extraction of walnut quinone from Juglans green peel.

Study on the Extraction Process of Herbal Pair Puerarin-Berberine by Plackett-Burman Design and Box-Behnken Response Surface Methodology / 中国药师

Objective:To optimize the alcohol extraction process of herbal pair puerarin-berberine.Methods:Based on the etha-nol reflux extraction,the extraction quantity of total flavonoids,total alkaloid,puerarin and berberine hydrochloride were used as the e-valuation index,and the independent variables included the drug particle,ratio of solid to liquid, ethanol concentration, reflux dura-tion and reflux times. Significance analysis was evaluated by Plackett-Burman design,and then the extraction process was optimized by Box-Behnken response surface methodology.Results:The optimal extraction conditions of drug pair puerarin-berberine were as follows:the drug particle was 80 mesh,the ratio of solid to liquid was 1:13,the ethanol concentration was 75%,the reflux time was 60 min, and the reflux times was 4. Under the above conditions, the extraction quantity of total flavonoids, alkaloid, puerarin and berberine hydrochloride was 120.34,56.99,109.63 and 39.26 mg ·ml-1, respectively.Conclusion: The extraction process of herbal pair puerarin-berberine is reasonable and feasible optimized by Plackett-Burman design and Box-Behnken response surface methodology.

Preparation and Quality Evaluation of Olanzapine Oral Disintegrating Films / 中国药师

Objective:To prepare olanzapine oral disintegrating films and evaluate its quality .Methods:The formula of olanzap-ine oral disintegrating films was optimized by Box-Behnken response surface methodology , the effects of the amount of HPMC and PEG400 were selected as the independent variables , and the tensile strength ,the elongation rate and the drug dissolution at 10 min were used as the dependent variables .The tensile strength , elongation rate , folding endurance , disintegration time and drug dissolution of olanzapine oral disintegrating films were evaluated and the in vitro dissolution was compared with that of the marketed olanzapine oral disintegrating tablets .Results:The optimal formula of olanzapine oral disintegrating films was as follows: the amount of HPMC was 11.0％and the amount of PEG400 was 2.3％.The oral disintegrating films had good film-forming performance, high hardness and flexibility, and could quickly disintegrate in 50 s with fast drug dissolution , and the in vitro dissolution was similar to the marketed olanzapine oral disintegrating tablets .Conclusion: The formula of olanzapine oral disintegrating films is reasonable , the preparation process is feasible , and the quality is stable and controlled , which is worthy of further development .

Optimization of Extraction Technology of Protein from Cryptotympana pustulata and in vitro Antioxidant Activity Study / 中国药房

OBJECTIVE:To optimize extraction technology of protein from Cryptotympana pustulata and investigate its in vitro antioxidant activity,so as to provide reference for further research of protein from C. pustulata. METHODS:Using extraction amount of protein as response value,based on single factor test,Box-Behnken response surface methodology was used to optimize the ratio of liquid to material,ultraonic time and extraction times.Validation test was conducted. Using Vitamin C(VC)as positive control, in vitro antioxidant activity of protein from C. pustulata was evaluated by using scavenging rate of 1, 1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2′-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid)(ABTS)free radical as index. RESULTS:The optimal extraction condition of protein from C.pustulata was as follows as the ratio of liquid to material 28:1(mL/g), ultrasonic time of 65 min,extracting for twice. In validation test,average extraction amount of protein from C. pustulata was 65.45 mg/g(RSD=1.68%,n=3),relative error of which to predicted value was 5.48%. The protein from C. pustulata showed strong scavenging effect on ABTS and DPPH free radicals. When the concentration of protein from C. slough was 0.2 mg/mL,and the scavenging rate of it to ABTS free radicals was 97%,the effect of which was similar to VC.The protein from C. pustulata showed weak scavenging ability to DPPH free radical,IC50was 0.96 mg/mL,the effect of which was not as good as VC. CONCLUSIONS:The extraction technology of protein from C. pustulata optimized by Box-Behnken response surface methodology shows high accuracy and good reliability.The protein from C.pustulata shows certain antioxidant activity in vitro.

Optimization of Extraction Process of Berberine Hydrochloride from Sanhuang Diyu Oil by Box-Benhnken Response Surface Methodology / 中国药师

Objective:To optimize the extraction process of berberine hydrochloride from Sanhuang Diyu oil by Box-Benhnken re-sponse surface methodology. Methods:The extraction process was optimized with the size of each medicine ( X1 ) , the liquid-solid ra-tio ( X2 ) and the extraction time ( X3 ) as the independent variables and berberine hydrochloride extraction amount ( Y) as the depend-ent variable, and the effects of variables and their interactions on the extraction efficiency were studied. Results:The experiment results indicated that the optimal extraction conditions were as follows:the size of each medicine was 60 meshes, the liquid-solid ratio was 18, and the extraction time was 1. 5 h. Under the above conditions, 3 batches of berberine hydrochloride from Sanhuang Diyu oil were ex-tracted. The average extraction rate of berberine hydrochloride was (16.6 ±0.6) mg·g-1(n =3). Conclusion: The extraction process of Sanhuang Diyu oil optimized by Box-Behnken response surface methodology is simple, stable and predictable.

Extraction Process Optimization of Total Flavonoids from Chloranthus Japonicus sieb by Box-Behnken Re-sponse Surface Methodology / 中国药师

Objective:To optimize the extraction process of total flavonoids from Chloranthus japonicus sieb by Box-Behnken re-sponse surface methodology. Methods:The independent variables were the ethanol concentration ( X1 ) , liquid-solid ratio ( X2 ) and extraction time ( X3 ) , the dependent variable was the extraction amount of total flavonoids ( Y) , and the extraction process was opti-mized by Box-Behnken response surface methodology. Results: The results showed that the optimal extraction conditions for total fla-vonoids from Chloranthus japonicus sieb were as follows: the ethanol concentration was 54. 8%, the liquid-solid ratio was 13. 6, and the extraction time was 2. 0 h. The verified extraction process parameters of three batches showed that the relative error between the ex-perimental values and those predicted from the regression model was -2. 34%. Conclusion:The optimal extraction process parameters are simple and more convenient with higher precision for the extraction of total flavonoids from Chloranthus japonicus sieb.

Preparation and characterization of epigallocatechin-3-gallate chitosan nanoparticles / 中草药

Objective: To prepare the epigallocatechin-3-gallate (EGCG) chitosan nanoparticles (CS-NPs) and investigate their physicochemical properties. Methods: The EGCG-CS-NPs were prepared by ion gelation method. The formulation variables were optimized by Box-Behnken Design (BBD) of response surface methodology (RSM) of CS concentration (X1), sodium tripolyphosphate concentration (X2), and EGCG concentration (X3) as independent variables and encapsulation efficiency (Y1,%) and particle size (Y2, nm) as dependent variables. The optimized CS-NPs were characterized for encapsulation efficiency (EE), particle size, Zeta potential, morphology, and in vitro drug release behavior of EGCG-CS-NPs were studied. Results: An optimal EGCG-CS-NPs consisting of CS concentration as 2.6 g/L, sodium tripolyphosphate concentration as 1.5 g/L and EGCG concentration as 2.7 g/L. For EE, particle size, Zeta potential of EGCG-CS-NPs were found to be (85.8±3.1)%, (102.2±27.1) nm, and (25.5±4.1) mV, respectively. The CS-NPs were found to be small and spherical as seen in transmission electron microscopy (TEM). The in vitro release data proved that the drug release was steady within 24 h (pH 4.5 PBS). Conclusion: Through optimizing the formulation, we obtain the uniform EGCG-CS-NPs with in vitro sustained-release behavior. This work is useful for the further research on pharmacodynamics of EGCG-CS-NPs.

Formulation Optimization of Indomethacin-loading Solid Lipid Nanoparticles by Box-Behnken Response Surface Methodology / 中国药房

OBJECTIVE:To optimize the formulation of indomethacin-loading solid lipid nanoparticle(SLN). METHODS:Us-ing indomethacin as model drug,glyceryl behenate as oil phase,poloxamer 188 and polyethylene glycol-12-hydroxystearic acid as emulsifier,with turbidity,entrapment efficiency and drug loading amount as index,Box-Behnken response surface methodology was used to optimize the amount of oil phase,emulsifier-oil phase ratio,drug-oil phase ratio. The physicochemical properties of SLNs were characterized by SEM and DSC. RESULTS:The optimal formulation was as follows as oil phase of 0.91%,emulsifier-oil ratio of 1∶1,drug-oil phase ratio of 1∶5. The turbidity,entrapment efficiency and drug loading amount of prepared nanoparticle were 1 025-1 030 NTU,98.94%-99.08%,2.43%-2.46%,respectively;particle size and polydispersity index(PDI)were 181.5-182.3 nm and 0.340-0.341(n=3). The results of DSC showed that indomethacin was not present in crystalline state dispersed into SLNs. CONCLUSIONS:The optimal formulation is screened successfully,and indomethacin-loaded SLNs have been prepared.

Optimization of Ultrasonic-assisted Extraction Process of Tremella Polysaccharides Based on Box-Benhnken Response Surface Methodology / 中国药师

Objective:To optimize the ultrasonic-assisted extraction technology of polysaccharide from Tremella by Box-Benhnken response surface methodology .Methods:The single-factor extraction tests and response surface analysis were employed to optimize the technology conditions , including ultrasonic power , ultrasonic time and liquid/solid ratio.Results:The experiment results indicated that the optimal extraction conditions were ultrasonic power of 360 W, ultrasonic time of 23 min and liquid/solid ratio of 45 ∶1 ( ml· g-1 ) . Under the conditions , 6 batches of polysaccharide from Tremella were extracted .The average extraction rate of Tremella polysaccharides was 20.4%±1.8%(n=6).Conclusion: The ultrasonic-assisted extraction process of Tremella polysaccharide using Box-Behnken response surface methodology is simple with good predictability .