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OBJECTIVE To prepare Leonurine hydrochloride tablets and evaluate the quality. METHODS The wet granulation technology was adopted ；leonurine hydrochloride was used as the crude drug ，and the types of fillers ，disintegrants，binders and lubricants were screened by single-factor experiments. Combined with orthogonal experiments ，using the cumulative dissolution rate within 15 minutes（using water as dissolution media ）as index ，the proportion of disintegrants ，the mass fraction of binder solution，and the proportion of lubricants were screened and verified. The in vitro dissolution behavior of the prepared Leonurine hydrochloride tablets （dissolution media were hydrochloric acid solution of pH 1.2，acetic acid-sodium acetate solution of pH 4.5， phosphate buffer solution of pH 6.8，water），tablet appearance ，hardness，friability and content uniformity were tested according to the general principles in 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. RESULTS The optimal formulation of Leonurine hydrochloride tablets included leonurine hydrochloride crude drug of 500 mg，dextrin of 9 250 mg，crosslinking polyving y- pyrrolidone of 200 mg，magnesium stearate of 50 mg，1％ hydroxypropyl methyl cellulose solution of 4 mL. The average 15-minute cumulative dissolution rate of the three batches of tablets was 81.25％（RSD＝1.12％，n＝3）. In above 4 dissolution media，the dissolution equilibrium of prepared tablets could be reached within 30 minutes，and the cumulative dissolution rates exceeded 85％. The prepared tablets had uniform beige in color ，smooth surface ，complete edge ，no mottle ，spot，foreign matter ， etc.，hardness of 57.3 N（n＝6），weight loss rate of 0.15％. The content uniformity was in accordance with relevant provisions in 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. CONCLUSIONS Leonurine hydrochloride tablets are successfully prepared ， and the quality comply with relevant regulations.
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Objective: Response surface methodology was used to optimize the purification process of naringin from Acanthopanax evodiaefolius leaves by polyamide resin. Methods: The optimum technological conditions for the purification of naringin in the leaves of Acanthopanax evodiaefolius were screened by single factor investigation and response surface design with five factors, including the concentration of sample, sample loading, the elution system, the amount of eluent, and the flow rate. Results: The optimum purification conditions of naringin in the leaves of A. evodiaefolius were as follow: the concentration of the sample was 4.0 mg/mL, the sample volume was 3.5 BV, the elution system was 30% methanol, the eluant volume was 3.0 BV, and the elution flow rate was 8.0 BV/h. Under this condition, the purity of naringin was improved from 5.08% to 56.12%, and the yield was 41.69%. And mass fraction reached more than 90% after recrystallization, which met the requirements of pharmaceutical raw materials. Conclusion: Purification of naringin from the leaves of A. evodiaefolius by polyamide resin chromatography has the advantages of good purification effect, simple operation, high efficiency, and good stability, which can be used for industrial production.
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Objective To screen the macroporous adsorption resin suitable for the separation and purification of total flavonoids from Litchi Semen, and the purification process parameters were established to prepare the total flavonoids of Litchi Semen in accordance with the requirements of effective parts of Chinese materia medica, which laid the foundation for the development of the total flavonoids of Litchi Semen into five new Chinese medicines. Methods The macroporous adsorption resin for purifying the total flavonoids of Litchi Semen by static adsorption-elution test was used. Based on the single factor test, the comprehensive score of adsorption rate was used as the index to investigate the volume fraction of ethanol, the mass concentration of the sample, and the sample solution pH, diameter to height ratio, upper column volume, upper column flow rate, eluent concentration, eluent volume and elution flow rate on the purification process, and determine the optimal purification process parameters. Results The best process condition for separating the total flavonoids of Litchi Semen by AB-8 macroporous adsorption resin were as follows: the mass ratio of resin to medicinal material was 3:1, the concentration of the upper column sample solution was 4—6 mg/mL, sample flow rate was 1 mL/min, and the upper column volume was 2 BV, diameter to height ratio was 1∶12, pH of the sample solution was 2, first impurity removal by 20% ethanol 3 BV, and using 60% ethanol 3 BV for elution, elution flow rate was 4 mL/min. Conclusion AB-8 macroporous resin can be used to purify the total flavonoids of Litchi Semen under the established technological conditions. The mass fraction of total flavonoids in Litchi Semen increased from 29.22% to an average of 67.37%, and the solid content decreased from 1.25 g to 0.40 g. It indicates that the established purification process is stable and feasible, and can be used as a purification process condition for total flavonoids of Litchi Semen.
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Objective: To prepare pegylated long-circulating liposomes co-encapsulated by costunolide (Cos) and dehydrocostus lactone (DL), optimize the formulation and process, and evaluate the quality. Methods: The pegylated long-circulating liposomes co-encapsulated by Cos and DL were prepared by film hydration method. Single factor test and Box-Behnken response surface methodology were used to optimize the preparation process with encapsulation efficiency of Cos and DL as the index. The particle size, surface potential, encapsulation efficiency and in vitro release of the liposomes were evaluated. Results: The optimal preparation conditions were as follows: drug-to-lipid ratio was 0.14, ratio of cholesterol to phospholipid was 0.05, mPEG-2000-DSPE addition amount was 6%, hydration time was 30 min, and probe ultrasonic time was 4 min. The obtained liposome was round and uniform in distribution, with an average particle size of (104.8 ± 2.48) nm, a polydispersity index (PDI) of (0.245 ± 0.031), and a Zeta potential of (-9.7 ± 0.23) mV, the encapsulation efficiency of Cos and DL were (91.9 ± 2.6)% and (94.41 ± 1.23)%, respectively. Conclusion: The PEGylated long-circulating liposome prepared by the process and prescription optimization has good appearance and high encapsulation efficiency, which can meet the application requirements.
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Objective To prepare and characterize ursolic acid nanoparticles (UANs), and to investigate its improvement of equilibrium solubility and dissolution rate. Methods UANs were prepared by emulsion solvent evaporation method, and followed by freeze-drying. The organic phase was trichloromethane containing 30% ethanol, the aqueous phase is ultrapure water, poloxamer 188 was as surfactant and cryoprotectant. The optimal conditions for preparing nanoparticles were screened out using single-factor experiment. The particle size was used as the basis for optimization experiment. The following six main parameters had significant influences on particle size were picked out, including the concentration of poloxamer 188, volume ratio of organic to water phase, homogenate speed and homogenate time, as well as homogenization pressure and cycles. And then, dynamic light scattering equipment was used to analyze the mean particle size, the morphology of UANs powder obtained was presented by scan electronic micro-scope (SEM). The UANs weather and how changes in surface chemical character and physical structure was estimated by using X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The equilibrium solubility study and dissolution test were carried on raw ursolic acid (UA) and UANs. Results The optimal conditions of preparation UANs: 0.05% of poloxamer 188, 1:4 of volume ratio of organic to water phase, 7 000 r/min of homogenate speed for 2 min and a homogenization pressure of 50.0 MPa for 6 times. Based on the optimal conditions, the mean particle size was (157.5 ± 28.0) nm and Zeta potential of (20.33 ± 1.67) mV. Particle distribution of UANs illustrated that UA had been nanoscale with uniform particle size distribution. SEM showed that UANs were nearly spherical. By the XRD and DSC, we could acquaint UA in UANs had the same chemical structure as the raw UA but had been amorphous state. The result of solubility test figured that the equilibrium solubility of UANs was 13.48 times in SGF, 11.79 times in SIF and 23.99 times in deionized water than raw UA. The dissolution rate of UANs prepared by ESE method has been up to 14.72 times in SGF and 74.35 times in SIF. Conclusion This study indicates that the emulsion solvent evaporation method has an array of valued on improving water solubility of UA, and it will have benefit on enhancing oral bioavailability.
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Objective: To prepare diphenidol hydrochloride push-pull osmotic pump tablets and in-vestigate the influence of differ-ent factors on in-vitro drug release. Methods: The cumulative release of different formulas was detected. Using the cumulative release and similarity factor f2as the evaluation criterion, single factor experiment was applied to screen the core formula and coating process. Results: The drug release behavior was affected by the content of PEO in the drug containing layer, the content of NaCl and the weight gain of the coating layer. After the formula was optimized, the NaCl content in the drug containing layer was 10mg, the PEO-N10 con-tent was 15mg. In the push layer, the content of PEO-WSR303 was 60 mg, that of NaCl was 20 mg. The optimized coating liquid for-mula contained 1. 25 g·L-1PEG4000 and the coating weight gain was 7% of the core. The optimized formula fitted a zero-order equa-tion within 2-12h with the drug release equation of Q=6. 308t-2. 5037(r=0. 995 8). Conclusion: The preparation technology of di-phenidol hydrochloride push-pull osmotic pump tablets is stable, and the in-vitro drug release fits zero-order model.
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Objective: To investigate the isomerization law of aescins A, B, C, and D under different conditions and optimize the isomerization process. Methods: Using the conversion of aescin C and D, and the content of impurity as index, single factor experiment was applied to evaluate the effect trends of isomerization from three parameters including pH value, reaction temperature and time. Then, central composite design-response surface method was used to estimate the relationship between the dependent and independent variables and to validate the optimal conditions. Results: According to the single factor experiment, the effect trends of three parameters on conversion of aescins C and D were analogous, and the isomerization happened under the conditions as follows: pH value of 5.0-10.0, reaction temperature of 45-85℃, and reaction time of 0.25-8 h. Based on the central composite design, the optimal conditions were predicted as follows: pH value was 6.9, reaction temperature was 54℃ and reaction time was 7.4 h. Under such conditions, the experimental values showed on significant difference from the predicted values. Conclusion: The isomerization of aescins A, B, C, and D could show a certain law under different conditions, and the optimal isomerization process is stable and available, which could provide a scientific basis of regulating the proportion of aescins A, B, C, and D during industrial production.
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Objective: To establish the optimal prescription and technique for preparing zedoary turmeric oil (ZTO) microcapsule. Methods: Using the diameter of microcapsule, microcapsule form, and embedding rate as indexes, the ratio of capsule materials, ratio of core material and capsule material, content of dry matter, content of additive, speed of emulsifying, time of emulsifying, temperature of wind and the power of feed were studied. Results: The optimal conditions for preparation of spray drying of ZTO microcapsule were as follows: gum Arabic-gelatin (1.0∶1.0), core material-capsule material (0.30∶1.0), PEG6000 content of 2%, dry matter content of 20%; The optimal technique was as follows: The emulsion speed was 10 600 r/min, emulsifying time was 9 min, temperature of inlet air was 160 ℃, and feed power was 6%. According to the optimum experimental conditions, the microcapsule was round relatively, the surface density was well, the particle size of microcapsule appeared uniform distribution, most concentrates in 1.0—2.5 μm, and showed good normal distribution, the average particle size was 1.913 μm, the embedding rate could reach 75.4%. Conclusion: This experiment can increase the stability of ZTO, cover up its bad smell, and raise the utilization ratio of drugs, the repeatability is also good.
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Objective To optimize the purification technology of total flavonoids from the leaves of Acanthopanax henryi by macroporous resin. Methods Using the purity and yield of total flavonoids as indexes, the single factor experiment combined with response surface methodology (RSM) was used to optimize the purification technology. Results It showed that D101 macroporous resin had good adsorption and desorption effects. The optimal purification conditions were as follows: diameter height ratio was 1:10, the loading amount was 750 mg each 25 g D101 macroporous resin, the flow rate was 5 mL/min, and eluted by 130 mL 50% ethanol. Under the proposed conditions, the experimental purity of total flavonoids reached 75.87%, which was well matched with the predictive purity of 75.69%. And the yield of total flavone was 30.13%. Conclusion The results proved that D101 macroporous resin can purify the total flavonoids from the leaves of A. henryi and RSM could optimize the purification technology effectively.
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Objective To prepare solid dispersions (SD) of Polygonum cuspidatum extract (PCE) with the intention of improving the dissolution rate of its active ingredients in vitro and exploring the applicability of hot melt extrusion in SD of traditional Chinese medicine extract. Methods The SD of PCE were prepared via hot melt extrusion based on Eudragit EPO. The cumulative dissolution of resveratrol and emodin in the extract of PCE was used as an evaluation index, and the single factor experiment was optimized. Then physicochemical properties of the SD prepared by optimized process were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM). Results The optimized process was 120 r/min for screw speed, 160 ℃ for barrel temperature and liquid nitrogen cooling. Under the optimized conditions, the dissolution rate of resveratrol and emodin in the extract was significantly improved, and the drug was present in the amorphous state in the carrier. Conclusion Hot melt extrusion can prepare SD of PCE to improve the dissolution rate of resveratrol and emodin, which provided experimental reference and data support for the study ofpreparation of SD of traditional Chinese medicine by hot melt extrusion.
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Objective To screen the preparation process of 3,4,3″-trihydroxy p-terphenyl nanosuspension. Methods The nanosuspension was prepared in combination with the nanoprecipitation and microfluidization method. Taken the particle size for indicator, we investigated the stirring speed and precipitation temperature in the nanoprecipitation process, the homogeneous stress and cycles in the microfluidic process through single factor experiment. In addition, by factorial design, the variety and dosage of stabilizers are investigated. Results The excellent preparation condition of the nanosuspension are as follows: 0 ℃ for the precipitation temperature, 900 rpm for the stirring speed, 1600 bar for the microfluidization pressure and 12 times for cycles. The ingredient ratio for drug: poloxamer 188: lecithin is 1: 0.8: 0.8. Conclusion Through optimizing the preparation technology, we have successfully prepared nanosuspension with lower size , which will lay a foundation for further study.
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OBJECTIVE:To optimize the extraction technology of total saponins from Coreopsis tinctoria. METHODS:Etha-nol leaching technology was adopted. Based on single factor test,the extraction technology was optimized by orthogonal test using extraction temperature,ethanol volume fraction,extraction time,solid-liquid ratio as factors,extraction rate of total saponins as in-dex. The optimized technology was validated. RESULTS:The optimal technology was that ratio of solid to liquid was 1:30 (C. tinctoria-60% ethanol),extracting for 2 h at 50 ℃. Validation test showed that average extraction rate of total saponins was 6.8%(RSD=0.85%,n=3). CONCLUSIONS:The optimized technology can be used for the extraction of total saponins from C. tinc-toria and keep stable.
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This study was aimed to optimize the extraction technology of Shu-Feng Ding-Chuan(SFDC) granules in the Huang-Qin(HQ)group by Box-Behnken response surface methodology(RSM).With three major characteristic components (baicalin,praeruptorin A and solid content in extraction liquid),the effects of four factors,such as the concentration of ethanol,the dosage of ethanol,the duration of extraction and the extraction times,were investigated by the single factor experiment.Then,the range of parameters of key factors was further studied and explored by Box-Behnken RSM.The results of single factor experiment and Box-Behnken design showed that the optimum preparation conditionswere 8-fold 70% ethanol,extracted for 2 times,with 1.0 h per each time.Under these conditions,the transfer rates of baicalin and praeruptor in A were 89.57% and 87.90%,respectively.And the transfer rateof solid content was 32.35%.It was concluded that the single factor experiment combined with RSM can be used in theoptimization of extraction technology for SFDC granules in the HQ group.This technique wasstable and feasible,which provided scientific evidences for the industrial production.
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Objective To investigate the factors that influence the fermentation process of compound Chinese medicine and determining the optimum fermentation with single factor experiment and response surface methodology. Methods Through controlling the factors in the fermentation process of compound Chinese medicine (such as fermentation bacteria, fermentation time, fermentation temperature, inoculum amount, etc.), with its increase rate of total peak area as evaluation indicator, the alcohol extracts before and after fermentation were monitored and comparative evaluated by HPLC, and the optimum fermentation process was determined by response surface methodology. Results The fermentation process optimized by single factor experiment and response surface methodology was as follows:SZ-2 strain served as the fermentation bacteria, temperature was 33 ℃, inoculum amount was 4%, and time was 3.5 d, the average increase rate of total peak area was 31.24%. Conclusion HPLC can be used to identify and evaluate the fermentation of compound Chinese medicine under the different factors, and to clarify the optimal fermentation process by response surface methodology, which provide reference for the development of fermentation process.