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Objective Optimizing the extraction process of prescription medicinal materials of hospital preparation of compound Yangshe granules. Methods A high performance liquid chromatograph (HPLC) quantitative method was established for deacetyl asperulosidicacid methyl ester (DME) and ferulic acid (FC) of the active ingredient. Based on the content of DME, FC and the yield of extract, the extraction process of compound Yangshe granule extract was optimized using central composite design-response surface methodology. Results The established HPLC method of quantification of active components in compound Yangshe granules met the requirements of method validation. The optimal extraction process optimized by central composite design-response surface methodology were as follows: the weight of extraction solvent was 12 times of the medicinal slices, the alcohol concentration was 73% and the extraction time was 60 min. Conclusion In this study, the quantitative method of active components in compound Yangshe granule by HPLC has been successfully established, and the optimized extraction process is simple and easy to operate with good repeatability.
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Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.
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Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.
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OBJECTIVE：To establish t he metho d for the content determination of pulegone in Schizonepetae tenuifolia decoction pieces and its compound preparation. METHODS ：Hollow fiber liquid-phase microextraction coupled with HPLC （HF-LPME-HPLC） was adopted. Based on single factor tests ，HF-LPME condition of S. tenuifolia decoction pieces and its compound preparation （taking Compound S. tenuifolia granule as an expample ） was optimized by central composite design-response surface methodology using pulegone enrichment multiple as index ，with the concentration of sample phase solution （NaCl），extraction time and stirring speed as factors. Validation test was conducted. HPLC method was adopted to determine the content of pulegone. The determination was performed on Hypersil C 18 column with mobile phase consisted of methanol- 0.3％ phosphoric acid （gradient elution ）at the flow rate of 1.0 mL/min. The detection wavelength was set at 252 nm，the column temperature was 25 ℃. The sample size was 20 μL. The feasibility of HF-LPME-HPLC method established in this study was validated by using HPLC method stated in the item of S. tenuifolia decoction pieces in 2020 edition of Chinese Pharmacopoeia （part Ⅰ）as reference. RESULTS ：The optimum HF-LPME conditions included n-nonanol as the extraction solvent ，sample phase solution with 11％ NaCl and pH value of 7，stirring speed of 800 r/min，extraction time of 36 min. Results of HPLC methodology investigation showed that linear range of pulegone were 0.05-5 μg/mL（r＝0.999 0）. The limits of detection and quantitation were 0.4 and 1.3 ng/mL，respectively. RSDs of intra-day and inter-day precision were 1.8％-4.0％ and 1.5％-4.1％（n＝3），respectively. RSDs of reproducibility and stability tests （24 h）were all lower than 8％（n＝6）. Average recoveries of S. tenuifolia decoction pieces and Compound S. tenuifolia granule were 102.6％-105.1％ and 97.2％-102.3％，respectively；RSDs were not higher than 4.1％ and 6.2％（n＝3）. The average contents of pulegone in S. tenuifolia decoction pieces determined by pharmacopoeia method and established method were 0.84 mg/g（RSD＝4.3％ ，n＝3）and 0.87 mg/g（RSD＝5.5％ ，n＝3），respectively，with no significant difference （P＞0.05）. CONCLUSIONS ：The established HF-LPME-HPLC method can enrich and concentrate pulegone ， shows strong purification ability and high sensitivity ，and can be used to determine the contents of pulegone in S. tenuifolia decoction pieces and its compound preparation.
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OBJECTIVE: To design and evaluate the formula of Weisu microemulsion-ion sensitive gel. METHODS The prescription of microemulsion-ion sensitive gel was conducted on the basis of single factor method and pseudotemary phase diagram method combining with central composite design-response surface methodology. The final formulation was evaluated by particle size, viscosity, potential, contents of naringin, hesperidin and neohesperidin. RESULTS: The optimum prescription ratio of Weisu microemulsion-ion sensitive gel was as following:volatile oil 3 g, RH-40 9 g, PEG-400 3 g, 0.3% deacetylated gellan gum made into 333 mL microemulsion gel. The results of physicochemical properties showed that microemulsion gel appearance was clear. The particle diameter was 20.14 nm. The Zeta potential was -4.04 mV. pH value was 5.43. The contents of naringin, hesperidin and neohesperidin are respectively 6.122 4, 2.094 1, 4.277 mg•mL-1. CONCLUSION: The preparation process of Weisu microemulsion gel is reasonable and feasible. The prepared microemulsion gel is system are stable.
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OBJECTIVE: To prepare the ketoprofen microemulsion-based gel in order to expand its drug loading and increase the transdermal permeability. METHODS: The proportion range of oil phase/surfactant in ketoprofen microemulsion were screened by the pseudo-ternary phase diagram. Optimization of formulation for microemulsion gels was conducted by central composite design-response surface methodology with the cumulative permeation quantity across in vitro rat skin and time-lag as evaluation indexes.The transdermal performance of self prepared gel was compared with the commercially available gel. RESULTS: The optimal oil phase, surfactant and cosurfactant of ketoprofen microemulsion were oleic acid, polyoxy ethylene castor oil (EL-35) and ethanol, respectively.The optimal microemulsion formulation was 1.35% oleic acid, 10.8% EL-35, and 9% ethanol by central composite design experiment. The cumulative penetration quantity in 24 h reached 562.82 μg•cm-2 in vitro rat skin was 1.35 times as much as commercially available gel. CONCLUSION: The ketoprofen microemulsion-based gel prepared in this study has good permeability, which lay the foundation for development of the gel.
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OBJECTIVE：To optimize the formul ation of Polygala japonica cream，and to evaluate the quality of prepared cream. METHODS ：With centrifugal stability ，heat resistance stability and viscosity as evaluation indexes ，the weight coefficient was determined by analytic hierarchy process （AHP），criteria importance through intercriteria correlation （CRITIC）method and mixed weighted AHP-CRITIC ，and the comprehensive score was calculated. The amount of octadecyl alcohol ，hexadecanol and mixed emulsifier （polysorbate 60 mixed with glycerin monostearate at the mass ratio of 2.82）in the formulation of P. japonica cream were screened by central composite design-response surface methodology. The optimized formulation was validated. P. japonica cream prepared by the optimal preparation was evaluated in terms of apperance ，particle，pH，stability and rheological characteristics. RESULTS ：The weight coefficients of centrifugal stability ，heat resistance stability and viscosity were 0.428 5， 0.415 6 and 0.155 9 respectively，according to the mixed weighted AHP-CRITIC. The optimal formulations were 1.96 g of hexadecyl alcohol ，5.17 g of octadecyl alcohol ，2.48 g of mixed emulsifier ，1.83 g of polysorbate 60，0.65 g of glyceride monostearate，1 g of benzyl alcohol ，5 g of propylene glycol ，6 g of isopropyl myristate and 5 g of P. japonica extract，and then added water to 100 g. Prepared cream was a light yellow fluid paste with particle size of 0.5-2.5 μm and pH value of 6.5；the results of centrifugal test ，heat resistance test and cold resistance stability test showed that the cream had no oil-water separation or thickened paste. The prepared cream was shear-thinning non-Newtonian fluid. CONCLUSIONS ：P. japonica cream is prepared successfully，which shows good apperance ，particle，acidity and stability.
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Objective To avoid the accumulation of copper sulfide (CuS) nanoparticles, prepare and optimize CuS nanoparticles, analyze the factors affecting the particle size and evaluate their photothermal properties. Methods Based on the single factor study, central composite design-response surface methodology was used to optimize the CuS nanoparticle formulation process. The morphology, particle size stability, photothermal conversion efficiency, photothermal stability of optimized CuS nanoparticles were characterized. The toxicity of CuS nanoparticles on 4T1 breast cancer cells and HK2 kidney cells was evaluated by CCK-8 method. In vitro photothermal experiment was used to investigate the ability of CuS nanoparticles on killing 4T1 breast cancer cells. Results The average hydration dynamic diameter of optimized CuS nanoparticles was (10.53±1.63)nm, the actual particle size of CuS nanoparticles showed by TEM image was (3.10±0.81)nm. It had good particle size stability, good photothermal conversion efficiency and photothermal stability. Within the concentration range of 100 μg/ml and 150 μg/ml，it showed no significant toxicity on 4T1 breast cancer cells and HK2 kidney cells, indicating the good stability of CuS nanoparticles. In vitro photothermal therapy showed that CuS nanoparticles had good ability to kill 4T1 breast cancer cells by photothermal. Conclusion The prepared CuS nanoparticles have a small particle size (less than 6nm) and a good photothermal effect, which is expected to solve the problem of CuS nanoparticles accumulation in vivo and make it better for tumor treatment.
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Objective: To prepare nerve growth factor(NGF) temperature sensitive in situ gel and investigate its therapeutic effect on sciatic nerve injury of rats.Method: NGF thermosensitive gel was prepared and its prescription was optimized by central composite design-response surface methodology.Fifty rats were randomly divided into the normal group,model group,NGF injection group(10 mg·L-1),NGF low-dose(10 mg·L-1) and high-dose(20 mg·L-1) thermosensitive gel groups,and sciatic nerve injury model of rats was established.The effect of NGF thermosensitive gel on the injury of sciatic nerve were comprehensively examined by taking rat behavior,sciatic nerve function index(SFI),time of withdrawal reflex,wet weight ratio of gastrocnemius muscle,and histomorphological changes as indicators.Result: The gelation temperature of NGF thermosensitive gel was 35.2℃ after the formulation being optimized,which was in line with the standard for injection.Four-eight weeks after operation,the SFI and wet weight ratio of gastrocnemius muscle in rats of NGF high-dose thermosensitive gel group were significantly higher than those in the model group and NGF injection group,but its time of withdrawal reflex was significantly lower than those in the model group and NGF injection group,and the effect was in a dose-dependent manner.Arrangement of regenerated nerve fibers in sciatic nerve injury area of rats from NGF high-dose thermosensitive gel group was more tidy,dense and continuous than that of the model group.Conclusion: NGF thermosensitive gel can promote repair of sciatic nerve injury in rats.
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Objective: With Bletillae Rhizoma gelatin as the main film-forming materials, Erhuangsan was developed into a sustained-release double-layer membrane for vagina. Method: Taking hydroxypropyl methyl cellulose(HPMC) and Bletillae Rhizoma gelatin as the film-forming materials of Coptidis Rhizoma-Alumen membrane layer, sodium carboxymethyl cellulose(CMC-Na) and Bletillae Rhizoma gelatin as the film-forming materials of Catechu membrane layer, glycerol as plasticizer, Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane was prepared.Central composite design-response surface methodology was used to optimize formulation of this preparation with appearance quality score, adhesion force and in vitro cumulative release as indexes. Result: Optimum formulation of Catechu membrane layer was 1.61% of CMC-Na, 3.81% of Bletillae Rhizoma gelatin and 8.49% of glycerol;optimum formulation of Coptidis Rhizoma-Alumen membrane layer was 1.15% of HPMC, 3.41% of Bletillae Rhizoma gelatin and 10.02% of glycerol. Conclusion: The optimized formulation is stable and feasible.Erhuangsan Bletillae Rhizoma gelatin sustained release double-layer membrane has characteristics of advanced dosage form and convenient use, providing a feasible modern Chinese medicine preparation for treatment of cervical cancer, and accumulating data for the research of Chinese medicine film agent.
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Objective: The formulation of co-loaded docetaxel(DTX) and gambogic acid(GA) albumin nanoparticles(DTX-GA-BSA NPs) was optimized by central composite design-response surface methodology to prepare DTX-GA-BSA NPs, and its quality was evaluated. The optimal synergistic ratio of DTX and GA was screened by coefficient of drug interaction(CDI). Method: NabTM method was used to prepare DTX-GA-BSA NPs with bovine serum albumin(BSA) as the carrier material. Design-Expert 8.0.6 software was used to design the experiment and process the data, overall desirability(OD) of particle size and polydispersity index(PDI), encapsulation rate were taken as indexes. The particle size and Zeta potential of the nanoparticles were measured. Individual and synergistic inhibitory effects of DTX and GA on the proliferation of MGC-803 and HGC-27 cells were determined by methyl thiazolyl tetrazolium(MTT) assay, respectively. Result: The optimum prescription of DTX-GA-BSA NPs was as follows:BSA concentration of 5 g·L-1, water-oil phase volume ratio of 1:17, drug-loading ratio(mass ration of drug to carrier) of 1:10.The average particle size of DTX-GA-BSA NPs was 135.8 nm and PDI was 0.09, Zeta potential was -21.4 mV. The deviation between the predicted value and the observed value of the model was small, the model had good predictability. For MGC-803 cell, when the concentrations of DTX and GA were 0.004, 0.12 μmol·L-1, respectively(mass ratio of DTX to GA was 1:23), the CDI value was the smallest and the synergistic proliferation inhibition was the most significant. For HGC-27 cell, when the concentrations of DTX and GA were 0.004, 1 μmol·L-1, respectively(mass ratio of DTX to GA was 1:195), the synergistic proliferation inhibition was the most significant. Conclusion: The optimized formulation of DTX-GA-BSA NPs is stable and reliable. The established mathematical model has good predictive ability and practicability. DTX combined with GA has synergistic effect on MGC-803 and HGC-27 cells without concentration dependence.
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Objective:To prepare Lycii Fructus polysaccharide buccal tablets and investigate its immunomodulatory effect. Method:Taking the appearance, taste, hardness and disintegration time of the tablets as comprehensive evaluation index, based on single factor tests, central composite design-response surface methodology was adopted to optimize the prescription of Lycii Fructus polysaccharide buccal tablets with mass ratio of dextrin to mannitol, mass ratio of cyclamate to malic acid and dosage of sodium carboxymethyl starch (CMS-Na) as factors. Kunming mice were randomly divided into 5 groups, namely the Lycii Fructus polysaccharide buccal tablets low (100 mg·kg-1·d-1), medium (200 mg·kg-1·d-1) and high (300 mg·kg-1·d-1) dose groups, the normal group (0.9% normal saline, 300 mg·kg-1·d-1) and the positive medicine group (Cinengsu group, 300 mg·kg-1·d-1). The immunomodulatory effect of the buccal tablets were investigated by calculating immune organ index, monocyte-macrophage phagocytic index, serum hemolysin antibody level, and the voix pedis thickness difference of delayed hypersensitivity (DTH) of mice. Result:Optimal prescription for the buccal tablets was 80% of Lycii Fructus extract, 11.5% of dextrin-mannitol (1.2:1), 1% of cyclamate-malic acid (1:1), 0.5% of cream essence, 6.5% of CMS-Na, 0.5% of magnesium stearate, and appropriate amount of 80% ethanol. Under the optimal condition, the hardness of the buccal tablets was 11.83 kg, its disintegration time was 13.21 min, both of which were in line with the relevant provisions of the 2015 edition of Chinese Pharmacopoeia, and the buccal tablets had good appearance and taste. Compared with the normal group, medium and high dose groups of Lycii Fructus polysaccharide buccal tablets significantly increased thymus index, spleen index and phagocytic index of mice (PPPPPConclusion:The formulation process of the buccal tablets optimized by central composite design-response surface methodology is stable and feasible, and Lycii Fructus polysaccharide buccal tablets can improve the immune regulation function of normal mice, and this study can provide experimental basis for the development, utilization and clinical application of Lycii Fructus and Lycii Fructus polysaccharides.
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Objective: To investigate the significance of each influencing factor and optimize the process of extracting indirubin from Isatidis Folium by Plackett-Burman design combined with central composite design-response surface methodology (CCD-RSM). Methods: Plackett-Burman experimental design was used to screen the main influencing factors, and CCD-RSM was used to optimize the extraction process of indirubin. With the concentration of ethanol, the ratio of material to liquid, and the extraction time as independent variables and the extraction amount of indirubin as dependent variable, the optimum extraction process of indirubin from Isatidis Folium was predicted and analyzed by multiple linear regression and binomial fitting models with independent and dependent variables and the three-dimensional surface graph. Results; The optimal extraction process of indirubin was as follows: ethanol concentration 62%, solvent/sample ratio of 26, and extraction time 9 min. Under these conditions, the maximal extraction rate of indirubin was 4.37 mg/g which was consistent with model predictions. Conclusion: The optimal process is simple and convenient for extracting indirubin from Isatidis Folium with high precision, reproducibility, and predictability.
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Objective: Analytic hierarchy process (AHP) was used to establish a comprehensive evaluation method of multiple indexes of traditional Chinese medicine, and the best processing technology of Sarcandra glabra was optimized. Methods: On the basis of single factor experiment, the comprehensive score of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isofraxidin, astilbin and rosmarinic acid content was used as evaluation index by AHP, and drying temperature and drying time were used as influencing factors. The purification process of S. glabra leaves was determined by single factor investigation. Taking soaking time, soaking time, cutting length and drying temperature as influencing factors, the optimal cutting process of S. glabra stems was optimized by central composite design-response surface method. Multi-index analytic hierarchy process (AHP) was used to analyze and verify the optimal process. Results: The best processing technology of S. glabra stems was as follows: stem Rob water washed once, soaked in 12 times of water for 1 h, moistened and softened for 3 h, cut into 15 mm segments after taking out, and baked at 50 ℃ for 2 h; The processing method of leaves was as follows: leaf Rob water washed once and dried at 50 ℃ for 4 h; Then mixed the processed stems and leaves of S. glabra at 2:1. The deviation between the verification value and the prediction value of the comprehensive score of the optimal S. glabra stem by softening and cutting method was 4.70%. Conclusion: The processing technology is simple, stable and feasible. The obtained parameters can provide scientific basis for the research and production of S. glabra, and AHP can provide reference for the multi-index evaluation of traditional Chinese medicine.
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Objective: To integrate the toxic component of cantharidin (CTD) into a novel nanostructured lipid carrier (NLC) and optimize the cantharidin nanostructured lipid carrier (CTD-NLC) formulation process to reduce the toxicity of CTD and enhance its targeting. Methods: CTD-NLC was prepared by emulsified ultrasonic dispersion method. The encapsulation efficiency was determined by dialysis method. The average particle size, particle size distribution (polydispersity index, PDI), Zeta potential, encapsulation efficiency, and drug loading were taken as indicators. Univariate investigation and central composite design-response surface methodology (CCD-RSM) were used to optimize the prescription process of CTD-NLC. Multivariate quadratic fitting was used to evaluate the model equation between indicators and factors. The fitted equation was analyzed by the variance analysis and the optimal prescription was predicted by the resonse surface. Results: The optimized CTD-NLC prescriptions were as follow: mass of total lipid was 453.66 mg, solid to liquid lipid ratio of 1:2, total stable dose of 16.9 mg/mL, ratio of Pluronic F68 to egg yolk lecithin (Lipoid E PC S) of 3.88:1, with ultrasound for 30 min (working 2 s, stopping 2 s). The prepared CTD-NLC was clear clarification in appearance with light blue opalescence, the average particle size was (85.99 ± 0.49) nm, PDI was 0.280 ± 0.002, Zeta potential was (-8.21 ± 0.24) mV, encapsulation efficiency was (98.57 ± 0.05)%, and drug loading was (0.65 ± 0.01)%. Conclusion: The fitting model established by CCD-RSM is accurate and reliable. The optimized CTD-NLC distribution is concentrated, with high encapsulation efficiency and good physical stability. It lays a foundation for the subsequent in vitro and in vivo studies of CTD-NLC.
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Objective: To optimize the formulation of syringopicrosides poly (lactic-co-glycolic acid, PLGA) nanoparticles (Syr-NPs). Methods: Syr-NPs were prepared by nanoprecipitation method. The encapsulation efficiency (EE), drug loading (DL), average particle size and general evaluation "normalized value" were used as evaluation indexes. The central composite design was used to inspect the effects of the concentration of PLGA (A), the concentration of syringopicrosides (B), the ratio of aqueous phase to organic phase (C) on three evaluation indexes mentioned above and the "normalized value" ofgeneral evaluation. Prediction and analysis for selecting the best prescription condition were carried out by using the central composite design-response surface method. Results: The concentration of PLGA, the concentration of syringopicrosides and the ratio of aqueous phase to organic phase according to the optimized prescription were 9.63 mg/mL, 12.88 mg/mL and 1:9.46, respectively; And the EE, drug loading and average particle diameter of Syr-NPs prepared according to the optimized prescription were (27.86 ± 0.87)%, (7.02 ± 0.15)%, and (110.0 ± 1.20) nm, respectively. Conclusion: This method is stable and feasible and can be used to optimize the formulation and preparation process of syringopicrosides wrapped inside with PLGA nanoparticles.
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Objective: In order to solve the problem of ginkgolide B (GB) for preparing the intravenous injection dosage form, such as it’s low solubility, rapid elimination in vivo and poor stability in long-term storage, a novel biodegradable polysaccharide polymer was used as a carrier to encapsulate GB into nanoparticles with sustained-release profile, which then was freeze dried for keep its stability. Methods: GB nanoparticles (GB-NP) were prepared by coacervation method with hydrophilicity polymer. The Design-Expert 8.0 software was applied for experimental design. The formulation was finalized by investigating the concentration of GB, the mass ratio of GB to polymer, and the pH of the polymer solution with size and polydispersity indexas the evaluation parameters. The optimum formulation and technique were selected by response surface method. Then the nanoparticle suspension was further freeze dried and in vitro release behavior was tested in PBS containing 30% ethanol. Results: The optimum prescription conditions were as follows: the concentration of GB was 1.5 mg/mL, the ratio of GB mass to polymer mass was 0.1 and the polymer solution pH was set at 5.0. The entrapment efficiency was (99.64 ± 0.45)% with the drug loading ratio of (9.04 ± 0.04)%. Average particle size of GB-NP was (192.8 ± 2.8) nm with a preferable PDI of 0.18 ± 0.03. The freeze-drying conditions were described as follows: using 1% mannitol as freeze- drying supporting agent, the solution of GB-NP was pre-frozen for 12 h at −80 ℃ and dried for 24 h at −40 ℃. The release behavior of free GB was rapid with the cumulative release rate reaching (64.74 ± 3.95)% during the first hour, while the cumulative release rate of GB in nanoparticles was (36.90 ± 1.41)% during the first hour. Conclusion: The GB-NP using this special biodegradable polysaccharide polymer can improve GB’s dissolution behavior in water and make GB sustained release in vitro, which is beneficial for preparing GB’s intravenous injection dosage form.
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OBJECTIVE： To establish a method for determining the content of tetracaine hydrochloride （TCH） ethosomes， and to optimize the preparation technology. METHODS： The content of TCH was determined by HPLC. TCH ethosomes were prepared with injection-ultrasonic method. Using drug-loading amount， egg lecithin concentration and ethanol volume fraction as factor， encapsulation efficiency as index， central composite design-response surface methodology was used to optimize the prescription based on the single factor test. The prepared ethosomes were characterized and the stability was evaluated. RESULTS： The linear range of TCH was 10-100 μg/mL （r＝0.999 5）； the limit of quantification was 0.045 μg/mL， and detection limit was 0.021 μg/mL. RSD of precision， stability and repeatability tests were less than 2％. The recoveries ranged 97.80％-103.20％ （RSD＝0.36％， n＝9）. The optimal preparation technology included that the adding amount of TCH control was 1 mg； the concentration of egg lecithin was 7 mg/mL， and ethanol volume fraction was 33％. Under this technology， the average encapsulation efficiency was 64.50％ （n＝3）， the relative error of which from the predicted value （64.92％） was 0.64％. TCH ethosome was a clear blue liquid with a blue opalescence. Its appearance was spherical， its shape was round， smooth， uniform in size； the average particle size was （80.33±2.24） nm， and the average Zeta potential was （－22.6±1.33） mV. TCH ethosome was stable during 10 days under 4 ℃， sealed and protected from light. CONCLUSIONS： The optimal preparation process is stable and feasible. Established method is simple and rapid.
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OBJECTIVE： To prepare Magnolol nano-crystal suspension （MAG-NS）， and to conduct quality evaluation. METHODS： The preparation technology of MAG-NS was optimized by central composite design-response surface methodology with OD value of particle size and polydispersity coefficient as evaluation indexes， using volume ratio of organic phase to water phase， ratio of excipient to drug， concentration of magnolol as factors and conduct validation tests. The quality of MAG-NS prepared optimal technology was evaluated. RESULTS： Optimized technology included that the volume ratio of organic phase to water phase was 1 ∶ 5， mass ratio of excipient to drug was 4 ∶ 1， concentration of magnolol was 2 mg/mL. In 3 times of validation tests， average OD value was 0.940 0 （RSD＝0.08％）， relative error of which to predicted value 0.977 7 was 3.86％. magnolol nano-crystals of MAG-NS prepared by the optimal technology were spherical， uniform in size， smooth in surface， with particle size of （34.88±0.33） nm， polydispersity coefficient of 0.032±0.001 and drug loading amount of （17.83±0.92）％. CONCLUSIONS： Established preparation method is simple and feasible. Prepared MAG-NS is in line with quality requirements. It can provide reference for further development and utilization of MAG-NS.
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OBJECTIVE： To establish a methaod for content determination of doxorubicin hydrochloride nano-liposomes， and to optimize its preparation technology. METHODS： The contents of doxorubicin hydrochloride nano-liposomes was determined by UV spectrophotometry. The membrane dispersion method was used to prepare doxorubicin hydrochloride nano-liposomes. Using particle size， encapsulation efficiency and drug-loading amount as indexes， the weight ratio of phospholipid to drug （mg/mg）， the weight ratio of phospholipid to cholesterol （mg/mg） and ultrasonic time （min） as factors， central composite design-response surface methodology was used to optimize the preparation technology. The photothermal conversion effect of doxorubicin hydrochloride nano-liposomes was investigated by near infrared irradiation. RESULTS： The linear range of doxorubicin hydrochloride were 1.01-16.16 μg/mL（r＝0.999 7）； precision， stability and reproducibility tests were all in line with the requirments of Chinese Pharmacopoeia. The optimal preparation technology included that the weight ratio of phospholipid to drug was 13.30 ∶ 1（mg/mg）； the weight ratio of phospholipid to cholesterol was 4.09 ∶ 1 （mg/mg）； the ultrasonic time was 10 min. Under this technology， the particle size and drug-loading amount of doxorubicin hydrochloride nano-liposomes were （200.5±25.1） nm and （11.02±0.20）％， relative errors of which to predicted value （196.3 nm， 10.68％） were 1.82％ and 1.63％. The consistency between measured value and predicted value was good. Doxorubicin hydrochloride nano-liposomes exhibited concentration- dependent and time-dependent photothermal conversion characteristics under near infrared irradiation at 808 nm. CONCLUSIONS： Established method is simple and good accuracy. The optimized preparation technology is simple and feasible.