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The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.
Subject(s)
Polysorbates/chemistry , Flavonoids , Pueraria , Surface-Active Agents/chemistry , Ethanol , Emulsions , Particle Size , SolubilityABSTRACT
OBJECTIVE: To optimize the formulation of econazole solid lipid nanoparticles(E-SLN) by combining pseudo-ternary phase diagrams and central composite design-response surface methodology (CCD-RSM). METHODS: Econazole solubility in different solid lipids and the capacity of lipid emulsion were tested. The microemulsion region was obtained by the pseudo-ternary phase diagrams. Then the E-SLN were prepared by microemulsion method. Drug/lipid (X1), lipid/surfactant (X2) and surfactant/cosurfactant (X3) were taken as individual factors, the encapsulation efficiency (Y1), particle size (Y2), Zeta potential (Y3) were taken as the dependent factors. The possible optimum formulation was predicted by CCD-RSM and validated. RESULTS: Econazole could be dissolved in tripalmitic acid glyceride (TAG), monostearic acid glyceride, stearic acid and lauric acid glyceride. TAG had a good capacity of emulsion. The optimized formulation was econazole 0.06 g, glyceryl palmitate 0.48 g, Tween-80 1.194 g, glycerol 0.274 g and added water to 30 mL by CCD-RSM. According to the optimized formulation, the encapsulation efficiency, particle size and Zeta potential were (94.06±1.54)%, (18.88±0.38)nm and (3.53±0.01)mV, respectively. The deviation was less than 5%. CONCLUSION: The stable and ultra-small size E-SLN with high encapsulation efficiency could be obtained by combining pseudo-ternary phase diagrams and CCD-RSM.
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Objective: To optimize andrographolide pellet by using a quality by design (QbD) approach. Methods: Usingthe cumulative in vitro release as evaluation index, the single-factor investigation and hazard analysis were used to study the core and coating process of andrographolide colon-targeting pellets, and the central composite design-response surface method was used to optimize and predict the three key factors of plasticizer dosage, aging time, and coating weight gain. Results: The optimum coating process parameters were as following: plasticizer dosage of 3 g, coating weight gain of 20%, and aging time of 1 h. The process had been verified that the optimal formulation process had a cumulative in vitro release of 6.9% in the acid phase (0.1 mol/L HCl)-buffered salt phase (pH 6.0) and a cumulative in vitro release of more than 90% in the pH 7.2 buffered salt phase. Conclusion: It is feasible to apply the QbD concept optimization in the study of andrographolide colon-targeting pellets.
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Objective To optimize prescription and evaluate the quality of imperatorin lipid microspheres (ILM) by central composite design-response surface methodology (CCD-RSM), therefore to use the mean particle size, particle size distribution (polydispersity index, PDI) and Zeta potential as the primary indicator. Methods Mean particle size, particle size distribution and Zeta potential of lipid microspheres were measured to investigate the effect of the concentration of egg yolk lecithin, poloxamer and percentage of soybean oil in oil phase on the properties of ILM preparation. Mathematic relation between indicator and factor was constructed by binominal fitting. Then the response surface method according to the best mathematical model of evaluation indicators was used to make predictive analysis of the best prescription. Optimized prescription was used to prepare ILM and evaluate its quality. Results Optimized prescription was egg yolk lecithin 1.50 g, F68 0.35 g, and MCT 10 g. All items of optimized prescription were similar to target values. According to the optimized prescription, mean particle size of ILM was (165.00 ± 0.22) nm, particle size distribution was 0.046 ± 0.070, Zeta potential was (−30.30 ± 0.13) mV, encapsulation efficiency was about 90.09%, drug-loading rate was 1.0 mg/mL. Conclusion Due to the better predictability of constructed mathematical model, CCD-RSM can be applied to optimize prescription of lipid microspheres and the optimized ILM meet pharmacy requirements.
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Objective: To optimize the purification technology of saponins in steamed Panax notoginseng with macroporous resin. Methods: The main factors affecting the purification process were screened by failure mode and effects analysis (FMEA). The purification method with macroporous resin was optimized by central combination design-response surface method (CCD-RSM) based on the recovery and purity of saponins. In this experiment, the concentration of sample solution, loading volume, washing volume, ethanol concentration, and ethanol elution volume were used to investigate the purification of saponins in steamed P. notoginseng. Results: The optimized purification process with macroporous resin was as follows: maximum recovery (82.81%) and purity (77.24%) of saponins were obtained with the concentration of saponin solution of 11.22 mg/mL, loading volume of 4.97 BV, washing volume of 2 BV, ethanol concentration of 70%, and ethanol elution volume of 3.31 BV. Conclusion: The optimized purification process based on FMEA and CCD-RSM is convenient and stable, with high recovery and purity of saponins, which has a certain practical value.
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Objective: To optimize the processing technology of Hemsleya omeiensis processed by licorice juice. Methods: HPLC was employed to determine the content of hemslecin A.Taking content of hemslecin A as index, the orthogonal test was adopted to optimize the covered moistening time, drying-time, and processing temperature. And the central composite design-response surface methodology (CCD-RSM) was adapted to optimize moistening time and drying-time further. Results: The optimum processing technology of H. omeiensis by the orthogonal test was covered moistening time of 7 h, drying-time of 12 h, and processing temperature at 80℃. The optimum processing technology by CCD-RSM was covered moistening time of 7.48-8.56 h, drying-time of 12.06-13.12 h, and processing temperature at 80℃. Conclusion: The experimental design method is precise and the data are reliable with the model. It is the first time that H. omeiensis is processed with licorice juice. Besides, it establishes the processing technology of H. omeiensis and provides a theoretical basis for the processing technology of H. omeiensis with licorice juice.
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The purpose of this paper was to study the pre-mixed materials of emulsion gel. Accessories were screened and formula was designed with the most common use, low cost and simple process as the standards. Experiments were designed by central composite design-response surface methodology (ccd-rsm). 8.0.6 Trial Design-Expert was used for data processing and analysis, and subjective scores were used as the index to draw the three-dimensional effect surface and 2D contour maps. It was determined that the optimal ranges were A (carbomer 940)： 0.05-0.065 g; B (castor oil)： 1.00-1.12 mL; C (poly polysorbate-80)： 0.15 mL. The optimal formula was as follows： carbopol 0.057 5 g, castor oil 1.1 mL, polysorbate-80 0.15 mL. The formulated substrate was studied on its preliminary stability and rheology characteristics, such as viscosity and thixotropy. Then with the optimal formula as substrate, emulsion type gel was prepared respectively with 98% rutin, 98% berberine hydrochloride, and 98% berbamine hydrochloride as the main component. With 0.9% normal saline as the absorption solution, the results showed that the ransdermal flux of the three formulations of 1 h was all less than 1%. The results indicated that this substrate had the potential to be developed into a premixed material. The emulsion type gel matrix made from this formula had a good appearance, stability to certain extent, appropriate viscosity and thixotropy, and showed no skin irritation in 1 h.
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OBJECTIVE: To prepare the inclusion complex of Lignum dalbergia odorifera oil with hydroxyl-β-cyclodextrin (HP-β-CD), and to optimize the preparation process of it. METHODS: The inclusion complex was prepared by the stirring-freeze-dry meth od. The preparation process was optimized by central composite design-response surface method (CCD-RSM), with the colligation score which was calculated by the yield of inclusion, the utilization rate of volatile oil and the content of trans-nerolidol as index. The inclu sion complex was verified by phase-solubility method, DSC,UV and microscopical identification. RESULTS: The optimum inclusion technology was: inclusion solvent 5% ethanol, stirring rate 500 r·min-1, HP-β-CD to volatile oil 33:1, inclusion temperature 42℃, inclusion time 2.5 h. The formation of inclusion complex can change the solubility, optical and thermodynamic properties of volatile oil. CONCLUSION: The preparation process of inclusion complex of Lignum dalbergia odorifera oil with HP-β-CD optimized by CCD-RSM is reasonable and feasible, and provide a reliable experiment basis for its application.
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Objective The biological half-life in vivo of local anesthesia is short, high concentration in local tissue is in-clined to cause central nerve and cardiovascular toxicity due to the drug absorption into blood by blood vessels.The research was to pre-pare the poly ( lactide-co-glycolide) nanoparticle loaded with ropivacaine ( RVC-PLGA-NPS) , optimize its process, and determine its characteristics in vitro. Methods An oil-in-water emulsion solvent evaporation technique was adopted to prepare the RVC-PLGA-NPS.The formulation was optimized by central composite design/response surface method(CCD-RSM), with the encapsulation effi-ciency( EE) , drug loading( DL) and particle size as the indexes.Research was also made on itsin vitro release by fitting different model equations. Results The acquired nanoparticals were smooth, with the mean particle size (331.21±2.11) nm, DL (13.81±1.35)%and EE (74.82±2.53)%.The accumulative release rate of the nanoparticals was about 73%in 96 h, which showed that Higuchi func-tion fitted the release curve. Conclusion The RVC-PLGA-NPS made by emulsion solvent evaporation technique have obvious drug-release behaviour in vitro.
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OBJECTIVE: To optimize the formulations of Zizyphi Spinosi Semen flavonoid dropping pills by central composite design-response surface methodology. METHODS: Central composite design-response surface methodology was applied to optimize the preparation process with the dropping distance, dropping temperature, and cooling temperature as independent variables, while dependent variables were the variance of weight, spherical degree, and dissolution time. SPSS software was used to fit multivariate linear equation and second-order polynomial equation for experimental data. Response surface and contour plot were delineated according to best-fit mathematic models by Origin software, and the optimum formulation was selected by response surface. RESULTS: Quadratic multinomial model was better than multivariate linear model, and the regression coefficient was 0.981. The bias between the observed and predicted values of the optimum process was negligible, indicating the high predictability of the model. CONCLUSION: The model established by central composite design-response surface methodology and SPSS software is accurate for prediction and can be used to optimize the preparation process of Zizyphi Spinosi Semen flavonoids dropping pills.