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OBJECTIVE：To prepare Brevisc apine（BRE） nanocrystals，and to evaluate its quality. METHODS ：BRE nanocrystal suspensions were prepared by media milling method. The diameter and amount of grinding beads ，grinding time ，type and ratio of stabilizer ，BRE ratio were investigated to screen the optimal technology and formulation with particle size and polydispersity index （PDI） as evaluation indexes. Using morphology ，color，particle size and PDI of BRE nanocrystals as evaluation index ，different lyoprotectants （50％ mannitol，5％ glucose，5％ lactose）and without lyoprotectant were investigated to screen the optimal lyoprotectant. Particle size analyzer ，scanning electron microscope （SEM），X-Ray diffraction （XRPD）， differential scanning calorimeter （DSC）were used to evaluate the quality of BRE nanocrystals which was prepared with the optimal technology and formulation. RESULTS ：The optimal technology and formulation of BRE nanocrystals included that particle size of 0.6 mm zirconia beads with the amount of 450 g，grinding time of 1 h，stabilizer of 15％ Tween-80，BRE ratio of 25％，without lyoprotectant. Prepared BRE nanocrystals were yellow powder with loose texture and uniform color. The average particle size of BRE nanocrystals was （283.10±3.08）nm，average PDI was （0.212±0.021）and average Zeta potential was （－38.48±0.39）mV. BRE nanocrystals were rod-like crystals ，uniform in distribution and had no change in crystalline state. Accumulative dissolution of BRE nanocrystals were （90.37±1.22）％ within 20 min. Under the condition of （40±2）℃ temperature and （75±5）％ relative humidity，BRE nanocrystals remained stable after being kept away from light for 3 months. CONCLUSIONS ：Established preparation method of BRE nanocrystals is simple and feasible. Prepared BRE nanocrystals show good stablility and dissolution.
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Objective: To prepare and investigate the pharmaceutical characteristics of naringenin (NAR) nanocrystals. Methods: NAR nanocrystals were prepared by media milling combined with spray drying method. The mean particle size and polydispersity index (PDI) of NAR nanocrystals were analyzed by Malvern Zetasizer. The morphology of the nanoparticles was observed by scanning electron microscope (SEM). The crystalline state and the chemical structure of NAR before and after nanonization were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and fourier transform infrared spectrometry (FT-IR). Dissolution rate of NAR before and after nanonization were studied using rotary basket method. Results: The mean particle size of NAR nanocrystals was (400.7 ± 6.9) nm, and PDI value was 0.23. After nanonization, the crystalline state and chemical structure of NAR were not obviously altered, and the solubility was significantly increased (in pH 1.2 hydrochloric acid solution and pH 4.5 phosphate solution, P < 0.05; in pH 6.8 phosphate solution and water, P < 0.01). The dissolution was obviously improved, T50 and Td were visibly decreased (P < 0.01). Conclusion: The optimized process is stable and feasible for the preparation of NAR nanocrystals. NAR nanocrystals have a tiny and uniform particle size. After nanonization, NAR was still crystalline, the solubility and the dissolution were significantly increased, which can provide the basis for the further development of NAR.
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Objective To study the feasibility of preparing insoluble flavonoids nanosuspensions (NS) by miniaturized media milling. Methods The miniaturized media milling method was constructed with the magnetic stirrer, vial and zirconia beads as the power plant, milling chamber and milling media to prepare the nanosuspensions of four flavonoids: quercetin (QCT), baicalin (BCN), puerarin (PRN), and silymarin (SLR). The process of stirring speed, the amount of milling medium and the milling time were optimized with average particle size, polydispersity index (PDI) and stability index (SI) as indicators. Results The optimized process of stirring speed, the amount of milling medium and the milling time of QCT-NS, BCN-NS, PRN-NS and SLR-NS were QCT-NS 800 r/min, 8 h, 1:1, BCN-NS 800 r/min, 24 h, 1:1, PRN-NS 800 r/min, 24 h, 2:1, SLR-NS 800 r/min, 12 h, 1:1. The average particle sizes of QCT-NS, BCN-NS, PRN-NS and SLR-NS prepared with the optimized process were below 400 nm. The PDI of QCT-NS, BCN-NS and SLR-NS was below 0.3 (PRN-NS) and SI was above 0.75, the PDI and SI of PRN-NS were 0.41 and 0, respectively. Conclusion The miniaturized media milling methods for preparation of insoluble flavonoids NS is simple, stable and feasible, and it is worth for further study.
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AIM To prepare diosgenin nanosuspensions.METHODS The nanosuspensions prepared by media milling method were solidificated by freeze drying method.With particle size and polydispersity index (PDI) as evaluation indices,stabilizer kind,ratio of diosgenin to stabilizer,ratio of preliminary nanosuspension volume to grinding bead amount,milling time,lyoprotectant kind and its amount as influencing factors,single factor test was applied to screening preparation and solidification processes.The morphology of nanosuspensions was observed,then the particle sizes and polydispersity indices of nanosuspensions and freeze-dried powder were determined.RESULTS The optimal conditions were determined to be 6:1 for ratio of diosgenin to Pluronic F127 (stabilizer Ⅰ),50:1 for ratio of diogenin to sodium dodecyl sulfate (SDS,stabilizer Ⅱ),1:4 for ratio of preliminary nanosuspension volume to grinding bead amount,120 min for milling time,and 8％ PEG-6000 and 2％ mannitol as lyoprotectants.The average particle size and polydispersity index of rod-like or flaky nanosuspensions were (348.1 ±14.2) nm and 0.244 ± 0.059,respectively,which were lower than those of freeze-dried powder.At room temperature,the particle sizes of nanosuspensions and freeze-dried powder remained stable within 35 d and 3 months,respectively.CONCLUSION The physical stability of diosgenin freeze-dried powder is superior to that of its nanosuspensions,which can be used after being reconstituted.
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AIM To prepare diosgenin nanosuspensions.METHODS The nanosuspensions prepared by media milling method were solidificated by freeze drying method.With particle size and polydispersity index (PDI) as evaluation indices,stabilizer kind,ratio of diosgenin to stabilizer,ratio of preliminary nanosuspension volume to grinding bead amount,milling time,lyoprotectant kind and its amount as influencing factors,single factor test was applied to screening preparation and solidification processes.The morphology of nanosuspensions was observed,then the particle sizes and polydispersity indices of nanosuspensions and freeze-dried powder were determined.RESULTS The optimal conditions were determined to be 6:1 for ratio of diosgenin to Pluronic F127 (stabilizer Ⅰ),50:1 for ratio of diogenin to sodium dodecyl sulfate (SDS,stabilizer Ⅱ),1:4 for ratio of preliminary nanosuspension volume to grinding bead amount,120 min for milling time,and 8％ PEG-6000 and 2％ mannitol as lyoprotectants.The average particle size and polydispersity index of rod-like or flaky nanosuspensions were (348.1 ±14.2) nm and 0.244 ± 0.059,respectively,which were lower than those of freeze-dried powder.At room temperature,the particle sizes of nanosuspensions and freeze-dried powder remained stable within 35 d and 3 months,respectively.CONCLUSION The physical stability of diosgenin freeze-dried powder is superior to that of its nanosuspensions,which can be used after being reconstituted.