The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Calorimetry, Differential Scanning ; Desiccation ; Drug Compounding/methods* ; Drug Stability ; Silybin ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Technology ; X-Ray Diffraction

The present study explored the drying effect of new spiral vibration drying technology on Chinese medicinal pills with Liuwei Dihuang Pills, Zhuanggu Guanjie Pills, and Muxiang Shunqi Pills as model drugs. With the drying uniformity, drying time, energy consumption, pill split, dissolution time, and change of index components as evaluation indicators, the drying effect of spiral vibration drying technology on model drugs was evaluated and compared with traditional drying methods, such as hot air drying and vacuum drying in the oven. The dynamic changes of moisture in Liuwei Dihuang Pills with different drying time were investigated. Compared with the traditional drying methods in the oven(hot air drying and vacuum drying) at 80 ℃, the spiral vibration drying only took 80 min, shortened by 80%, with 10%-13% energy consumed. The results showed that the moisture of Liuwei Dihuang Pills was negatively related to the drying time. By virtue of multi-layer countercurrent drying and super resonant fluidization techniques, the new spiral vibration drying technology can significantly improve the drying quality of Chinese medicinal pills, improve the drying efficiency, and enhance the manufacturing capacity of Chinese medicinal pills. This study is expected to provide references for the innovation and development of new drying technology of Chinese medicinal pills.
China ; Desiccation ; Physical Therapy Modalities ; Technology ; Vibration

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

To verify the appropriate preparation process of extracts for the solid substance benchmark of Linggui Zhugan Decoction. The extracts were prepared by different preparation processes, namely the traditional process(process 1), the extract combined with volatile oil separated from traditional process extract liquid(process 2), the modern secondary reflux extraction process(process 3) and the process that volatile oil was extracted first, then prepared according to the traditional process, and combined with extract(process 4); based on the characteristic spectrum, index components of cinnamaldehyde, glycyrrhizin, ammonium glycyrrhizinate, cinnamic acid, and the dry extract rate of process 1, the differences and similarities of four extracts were compared. The results showed that the similarity of the characteristic spectrum of process 2, process 4 and process 1 were all greater than 0.97, while there was no significant difference for the content of 4 quality control components and dry extract rate; the similarity of the characteristic spectrum of process 3 and process 1 was 0.91, the absolute peak area of 13 out of 21 peaks and the relative peak area of 7 peaks increased significantly, and the content of 3 out of 4 quality control components and dry extract rate also significantly increased. In conclusion, the material standards of extracts by the process 2 and 4 are consistent with that of the traditional process, so the two processes are suitable.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Glycyrrhizic Acid ; Oils, Volatile ; Quality Control ; Reference Standards

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.
Administration, Oral ; Biological Availability ; Caco-2 Cells ; Drug Delivery Systems ; Emulsions ; Humans ; Methylcellulose/analogs & derivatives* ; Nanoparticles ; Particle Size ; Silybin ; Solubility

Objective:To investigate the relationship between phase behavior of curcumin （CUR） from self-nanoemulsion drug delivery system （SNEDDS） and stability of the formed nanoemulsion in artificial gastrointestinal fluid. Method:The growth rate of precipitation after dispersion of CUR-SNEDDS was expressed by the change tendency of CUR supersaturation-time curve. The effect of drug loading on crystal nucleation and growth was investigated by ultraviolet-visible spectrometry and polarized light microscope， respectively. X-ray powder diffraction （XRD） and differential scanning calorimetry （DSC） were used to analyze the precipitation forms of CUR-SNEDDS with different drug loading in artificial gastrointestinal fluid. At the same time， the effect of drug loading on the quality stability of nanoemulsion formed by CUR-SNEDDS in artificial gastrointestinal fluid was investigated. Result:In the artificial gastrointestinal fluid， with the increase of drug loading， the area under the supersaturation-time curve of CUR was increased （100% drug loading≈90% drug loading>75% drug loading）， the crystallization nucleation and growth rate were accelerated （100% drug loading>90% drug loading>75% drug loading）， the amorphous proportion in the precipitation composition decreased， the nanoemulsion droplets adhered and distributed unevenly， the particle size and dispersivity were increased. Conclusion:High drug loading promotes the nucleation and growth of crystals， and increases the proportion of crystal forms in the precipitation composition， which leads to the decrease in the stability of the formed nanoemulsion. Therefore， it is suggested that the drug loading of CUR-SNEDDS needs to be controlled below 90%.