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Objective To optimize the microwave-assisted extraction process of green tea polyphenols. Methods The extraction yield of tea polyphenols was figured up by building the standard curve of gallic acid and examining the concentration of tea polyphenols in green tea extract with the introduction of a correction factor. The effects of four single factor levels of microwave extraction time, microwave output power, liquid-to-material yield, and ethanol volume fraction on the extraction yield of tea polyphenols were primarily studied in this experiment. The response surface was applied to further optimize the extraction process of green tea polyphenols after exploring the appropriate range of four single factor levels. Results The optimal extraction process was as follows: extraction time 37 s, microwave output power 350 w, material - liquid yield 1∶45 (g/ml), ethanol volume fraction 55%, and the actual extraction yield of tea polyphenols was 25.65%, which was not much different from the theoretical value. Conclusion The microwave-assisted green tea polyphenol extraction process optimized by response surface methodology is time-saving and practicable, and the extraction yield is high.
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Central composite design (CCD) is one of the most commonly used design methods in response surface optimization and has been widely applied in the field of pharmaceutics to optimize preparations. On the 20th anniversary of the introduction of CCD into China, the paper reviews its application in domestic pharmaceutical researches. Based on the brief introduction of basic principle and operation steps of CCD, the mistakes emerging in the application of CCD are summarized, including conceptual confusion with Box-Behnken design and face-centered CCD as well as wrong designs. Besides, the issues concerning the selection of factors and responses are discussed. The article is helpful for researchers to comprehensively understand the CCD and facilitates the rational application of this method.
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OBJECTIVE To design N dodecanol modified docetaxel(DTX) prodrug, prepare nanostructured lipid carrier(NLC) and investigate in vitro antitumor activity and in vivo pharmacodynamic. METHODS Nanostructured lipid carrier (DNLC) encapsulating n-dodecanol-modified DTX prodrug was prepared by ultrasonic method. The formulation was optimized by single-factor experiment and response surface optimization. The accumulated rates of DTX degraded from DNLC in different media was evaluated by high performance liquid chromatography (HPLC). The morphology of DNLC was observed by transmission electron microscopy (TEM). The particle size and PDI of DNLC were determined by Malvern particle size analyzer. The long-term stability of the preparations was investigated. In vitro cytotoxicity of DNLC was measured by MTT method. In vivo pharmacodynamics of DNLC were performed in 4T1 tumor xenograft balb/c mice using saline and DTX-Sol as control. RESULTS n-Dodecanol-modified DTX prodrug was synthesized and used to prepare DNLC. The optimal formulation was as following: mass ratio of emulsifier to co-emulsifier (Km) of 1∶3, solid-liquid lipid ratio of 1.43∶1, drug-lipid ratio of 1∶10, the emulsifier concentration of 60 mg•mL-1, the temperature of 70 ℃ and the stirring speed of 800 r•min-1. DNLC had a round appearance and a uniform spherical shape. And the particle size and PDI remained substantially stable within 30 d. The accumulated rates of DTX degraded from DNLC in PBS (pH 7.4), PBS (pH 7.4) containing 10 mmol•L-1 DTT and 10 mmol•L-1 H2O2 was (9.07±0.01)%, (21.52±0.35)% and (96.72±4.12)% at 24 h, respectively. After incubation of DTX-Sol and DNLC with 4T1 cells for 72 h, IC50 of DTX-Sol and DNLC were (1.2±0.2) and (13.2±4.3)nmol•L-1, respectively. The cytotoxicity of DTX-Sol group was stronger than that of DNLC group. At the end of the pharmacodynamics, the tumor volumes of the mice in saline, DTX-Sol and DNLC groups were (1 930.39±215.20), (1 013.64±138.65), and (765.16±177.43)mm3, respectively. And the change percentage of body weight in saline, DTX-Sol and DNLC groups were (-19.69±4.44)%, (-14.85±3.61)% and (-2.61±1.70)%. There were significant differences in tumor volume and body weight between the DNLC and DTX-Sol group (P<0.05). CONCLUSION The prepared DNLC shows good stability, redox sensitivity, obvious anti-tumor effect and lower toxicity. These RESULTS could provide a new experimental basis for the development of DTX prodrug loaded nano-drug delivery system.
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Objective: To optimize the preparation technology of phospholipid complex of Carthamus tinctorius (safflower) extract and investigate its permeability. Methods: On the basis of single factor experiment, the preparation process was optimized by using the response surface analysis method, taking the compound rate of phospholipid complex of safflower extract as the index. It was characterized by UV-vis absorption spectrum and infrared spectrum. The modified Franz diffusion cell was used to evaluate the membrane permeability of safflower extract and phospholipid complex of safflower extract with different drug-lipid ratios in vitro. Results: The optimum preparation technology of phospholipid complex of safflower extract was as follows: methanol was used as compound solvent, the concentration of safflower extract was 5.0 mg/mL, and the mass ratio of phospholipid to phospholipid was 1∶1, the reaction time was 1.5 h, and the reaction temperature was 55 ℃. The results of transmembrane experiment showed that the 24-hour cumulative permeability (Q24) of safflower extract phospholipid complex with drug-fat ratio of 2, 1, and 0.5 was (15.07 ± 1.24), (15.61 ± 0.92), (21.94 ± 1.54), and (21.05 ± 1.39) μg/cm2, respectively. Conclusion: The optimized preparation process is reasonable and feasible, and the phospholipid complex of safflower extract can obviously improve its membrane permeability.
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Objective: To prepare Gualou-Xiebai intragastric floating pellets(18-24 mesh)by extrusion-spheronization method, and investigate their release characteristics in vitro. Methods: Using the floating time of pellets as indicator and the percentage of microcrystalline cellulose (MCC), octadecanol, hydroxypropyl methylcellulose- K4M (HPMC-K4M)and HPMC-K15M in the solid excipients of the prescription as affecting factors on the basis of single factor experiments, the formulation was optimized by star design-response surface optimization method. Taking the content of 3, 29-dibenzoyl karounitriol in the release medium as the index, the release rate of the pellets in vitro was determined and the release characteristics were explored. Results: The optimum prescription of these pellets was as follows: Gualou-Xiebai dry extract 25 g, MCC 6 g, octadecanol 11 g, HPMC-K4M 3 g, HPMC-K15M 11 g, 70% ethanol solution as wetting agent, and 40% polyvinylpyrrolidone(PVP-K30)solution as binder. The floating time in vitro of the pellets prepared by this prescription was 12 hours, and the cumulative release rate data fitted well with the first-order release model (r>0.97). Conclusion: The Gualou-Xiebai intragastric floating pellets prepared in this study had good floating property and sustained release effect, indicating that the preparation method is feasible.
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Extrusion-spheronisation method was used to prepare Rhus chinensis total phenolic acid pellets. The formula and preparation of R. chinensis total phenolic acid pellets were optimized. The formulas( drug loading capacity,diluent,wetting agent and anti-sticking agent) were determined by the single factor test with yield,appearance and performance as the indexes. The preparation was optimized by Box-Behnken design and response surface method,with the rate of extrusion,rate of spheronization and time of spheronization as the independent variables and the overall desirability value of yield,friability and roundness as the dependent variables. The optimal formula of pellets was as follows: drug loading capacity 28. 7%,MCC-lactose 9 ∶1,silicon dioxide as anti-sticking agent,and 60% ethanol as wetting agent. The optimal preparation was determined as follows: the rate of extrusion was 43 r·min-1,the rate of spheronization was 1 800 r·min-1,and the time of spheronization was 4 min. The absolute deviation between predicted value and estimated value under the conditions was less than 5. 0%,with a high degree of model fit. The preparation parameters obtained were accurate,reliable and reproducible. Under scanning electron microscopy( SEM),R. chinensis total phenolic acid pellets were uniform in diameter,round and smooth. The optimal formulation and process are stable and feasible for preparing R. chinensis total phenolic acid pellets.
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Drug Compounding , Methods , Hydroxybenzoates , Chemistry , Particle Size , Rhus , Chemistry , SolubilityABSTRACT
OBJECTIVE: To study the preparation process of pH-dependent delayed colon targeting pellets of astragalus polysaccharide. METHODS: Colon targeting agents of APS pellets were produced by extrusion-spheronization and fluid bed coating method and the best preparation technology was chosen by response surface optimization method. RESULTS: The ratio of pill core: APS powder-avicel-tannic acid-carboxymethylcellulose sodium was 25:15:8:2, the wetting agent was water, the rate of extrusion was 60 r·min-1, the rate of spheronization was 1 400 r·min-1, and the time of spheronization was 4 min. The best fluid bed coating condition was as follows the fan frequency was 29.50 Hz, the pressure of spray gun was 0.70 kg·cm-2, the rate of coating flow was 3 mL·min-1, and the colon coating weight was 15%. The release degree of pill for simulated gastric fluid in 2 h was 0%, The release degree of pill for artificial intestinal fluid in 3 h was less than 5%. The release degree of pill for artificial colon fluid in 2 h was release completely. CONCLUSION: The preparation method can be qpplied to the preparation of APS pellets, it's simplicity of operator and had good reproducibility, it can be applied to the industrial production.
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Objective: To optimize the preparation of β-cyclodextrin (β-CD) inclusion compound of forsythia oil and peppermint oil using the colloid mill method. Methods: With recovery ratio and inclusion rate of volatile oil-β-CD as evaluation indexes, the single factor test combining Box-Behnken response surface methodology was used to study the effects of β-CD-pure water ratio, β-CD-volatile oil ratio, and inclusion time on the inclusion process of volatile oil. Using TLC, IR spectrum, and microscopic image, the inclusion complexes were confirmed. Results: The optimum preparation conditions of inclusion compound were as follows: β-CD-pure water ratio was 1:3, mixture of forsythia oil and peppermint oil-β-CD ratio was 1:9, and the inclusion time was 25 min. The formation of inclusion complex was preliminary proved by TLC, IR spectrum, and microscopic image. Conclusion: The method is reasonable and feasible.
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Objective: Through the preparation of puerarin self-microemulsifying osmotic pump controlled-release capsule and controlled-release insoluble drug to improve the bioavailability of puerarin. Methods: Through the construction of self-microemulsifying osmotic pump controlled-release capsule of puerarin to do quantitative determination using microemulsion chromatography method. Through the single factor investigation, the three influencing factors were determined: dosage of penetration enhancer NaCl, coating weight, and porogen PEG 400. The optimal prescription was predicted by using central composite design and response surface optimization. Results: The formulation for puerarin self-microemulsifying osmotic pump controlled-release capsule was puerarin 0.07 g, ethyloleate 0.25 g, Polysorbate 80 0.45 g, PEG 400 0.3 g, mannitol 1.07 g, and NaCl 1.07 g. Based on the release of preparation and prediction of prescriptions in 4, 8, and 12 h, the controlled-release capsule conformed to the zero-order release model. Conclusion: Self-microemulsifying osmotic pump capsule could solve the controlled-release of insoluble drugs.