[Co-amorphous technology to improve dissolution and physical stability of silybin].

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.

[Effects of HPMCAS MF on absorption of silybin from supersaturable self-nanoemulsifying drug delivery system].

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.

Improvement of the bioavailability of curcumin by a supersaturatable self nanoemulsifying drug delivery system with incorporation of a hydrophilic polymer: in vitro and in vivo characterisation.

OBJECTIVES: The current study was focused on preparing curcumin (CUR) supersaturated self-nano-emulsion (PI-CUR-SNEDDS) using hydrophilic polymer and to study the influence of polymer precipitation inhibitor on the physicochemical and biopharmaceutical properties of the PI-CUR-SNEDDS. METHODS: PI-CUR-SNEDDS were prepared using hydrophilic polymer in order to maintain the supersaturation of CUR in nano-emulsion solution, artificial gastrointestinal fluid (AGF), and the precipitates formed, and characterised by in vitro dispersion tests, in vitro intestinal absorption and in vivo pharmacokinetic and compared with CUR-SNEDDS. KEY FINDINGS: PI-CUR-SNEDDS prepared with 2% hydroxypropyl methylcellulose 55-60 (HPMC55-60) as precipitation inhibitor (PI) significantly improved the viscosity, physical stability and CUR's equilibrium solubility of nanoemulsion. HPMC55-60 and CUR interact in AGF through intermolecular interactions, form hydrogen bonds, and produce amorphous precipitates. Compared with CUR-SNEDDS, the proportion of CUR in the hydrophilic phase increased by about 3-fold, and apparent permeability coefficient (Papp) in duodenum, jejunum, ileum, and colon increased by 2.30, 3.65, 1.54 and 2.08-fold, respectively, and the area under the plasma concentration-time curve0-12h of PI-CUR-SNEDDS also increased by 3.50-fold. CONCLUSIONS: Our results suggested that HPMC55-60 maintained the CUR supersaturation state by forming hydrogen bonds with CUR, increasing the solution's viscosity and drug solubilisation, thus improving the absorption and bioavailability of CUR.

[Study on preparation extraction process of Linggui Zhugan Decoction].

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.

Effect of Baizhu (Rhizoma Atractylodis Macrocephalae) extract on intestinal absorption of brucine and strychnine in vitro and in situ.

OBJECTIVE: To investigate the antagonistic effect of the extract of Baizhu (Rhizoma Atractylodis Macrocephalae) (RAM) on the intestinal absorption of brucine and strychnine in Strychnos nux-vomica (NUX) and propose the mechanism of these effects. METHODS: The apparent permeability value (Papp) and absorption rate constant (Ka) were chosen as indices. The everted intestinal sac model and in situ single-pass intestinal perfusion model were used to study the effects of the RAM extract on the absorption of brucine and strychnine. To confirm the results, the brucine and strychnine concentrations in hepatic portal venous blood were determined. Western blotting was used to study P-glycoprotein (P-gp) expression in the Caco-2 cell line. RESULTS: Papp and Ka of brucine and strychnine were significantly increased in the presence of a P-gp inhibitor, but no significant increase was noted in the presence of a tight junction regulator. The RAM extract inhibited the absorption of brucine and strychnine and enhanced P-gp expression. CONCLUSION: The primary absorption mechanism for brucine and strychnine is passive transport, which is affected by P-gp.

[Key physical parameters of hawthorn leaf granules by stepwise regression analysis method].

The purpose of this study was to investigate the effect of key physical properties of hawthorn leaf granule on its dissolution behavior. Hawthorn leaves extract was utilized as a model drug. The extract was mixed with microcrystalline cellulose or starch with the same ratio by using different methods. Appropriate amount of lubricant and disintegrating agent was added into part of the mixed powder, and then the granules were prepared by using extrusion granulation and high shear granulation. The granules dissolution behavior was evaluated by using equilibrium dissolution quantity and dissolution rate constant of the hypericin as the indicators. Then the effect of physical properties on dissolution behavior was analyzed through the stepwise regression analysis method. The equilibrium dissolution quantity of hypericin and adsorption heat constant in hawthorn leaves were positively correlated with the monolayer adsorption capacity and negatively correlated with the moisture absorption rate constant. The dissolution rate constants were decreased with the increase of Hausner rate, monolayer adsorption capacity and adsorption heat constant, and were increased with the increase of Carr index and specific surface area. Adsorption heat constant, monolayer adsorption capacity, moisture absorption rate constant, Carr index and specific surface area were the key physical properties of hawthorn leaf granule to affect its dissolution behavior.

[Improvement of powder flowability and hygroscopicity of traditional Chinese medicine extract by surface coating modification technology].

To study the improvement of powder flowability and hygroscopicity of traditional Chinese medicine extract by surface coating modification technology. The 1% hydrophobic silica nanoparticles were used as surface modifier, and andrographis extract powder was taken as a model drug. Three different techniques were used for coating model drugs, with angle of repose, compressibility, flat angle and cohesion as the comprehensive evaluation indexes for the powder flowability. The powder particle size and the size distribution were measured by Mastersizer 2000. FEI scanning electron microscope was used to observe the surface morphology and structure of the powder. The percentage of Si element on the powder surface was measured by energy dispersive spectrometer. The hygroscopicity of powder was determined by Chinese pharmacopoeia method. All of the three techniques can improve the flowability of powder extract. In particular, hygroscopicity of extract powder can also be improved by dispersion and then high-speed mixing, which can produce a higher percentage of Si element on the powder surface. The improvement principle may be correlated with a modifier adhered to the powder surface.

[Study on key physical properties of granulated products of Andrographis mixed powder by high-speed mixing wet method].

The impact of key physical properties on granulated products by the high-speed mixing wet method was studied. Andrographis extracts were utilized as the model drug. Four processing methods were adopted to prepare mixed powder of microcrystalline cellulose (MCC) and starch with the mass ratio 1:0.5, 1:1 and 1:2 by the high-speed mixing wet method. The properties of the prepared granules were evaluated with such indexes as granule yield, the ratio of lumps and fine powder, granule-AOR and granule-HR. The impact of key physical properties on granulated products was analyzed through stepwise regression analysis. The results showed that angle of repose, moisture content, pore volume, density and contact angle with water were key physical properties of the powder. The key physical properties of Chinese medical extracts powder are the important factor impacting granulated products made by the high-speed mixing wet method. In this study, the impact of key physical properties on granulated products of Chinese medical extracts was analyzed from the physical angle.

Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP.

AIM OF STUDY: Yuanhu Zhitong prescription that consists of Corydalis yanhusuo and Radix Angelicae dahuricae has been used for the treatment of gastralgia, costalgia, headache and dysmenorrhea in Traditional Chinese Medicine. Our previous studies demonstrated that Corydalis alkaloid (CA, derived from the root of Corydalis yanhusu) had potent analgesic properties, and the total coumarins of Angelica dahurica (Cou) and volatile oil (VO) that derived from the root of Radix Angelicae dahuricae all could increase the analgesic effect of CA. The major objective of this paper was to investigate the mechanism that leading the analgesia of CA increased by Cou and (or) VO. MATERIALS AND METHODS: The relationship between analgesic effect of CA and the plasma concentration of Dl-tetrahydropalmatine (dl-THP, active component of CA) was assayed in mice writhing test. The CA (34, 68 and 134 mg/kg) reduced the nociception by acetic acid intraperitoneal injection in a dose-dependent manner, and there was a significant linear relationship between the analgesic effect of CA and the plasma concentration of dl-THP. Then the plasma concentration of dl-THP at different time intervals in rats after oral administration of CA, CA-Cou, CA-VO and CA-Cou-VO were examined by using HPLC. RESULTS AND CONCLUSION: The results indicated that Cou and (or) VO raised the plasma concentration of dl-THP prominently. In conclusion, the reason that Radix Angelica dahurica extracts reinforced the analgesic effects of Corydalis alkaloid was related to the improvement of the plasma concentration of dl-THP.

[Comparison of microwave-assisted and conventional extraction of Corydalis yanhusuo].

OBJECTIVE: To compare the extraction yield and economic cost in the microwave-assisted extraction and conventional extraction of Corydalis yanhusuo. METHODS: Both of the extractions of Corydalis yanhusuo were optimized by orthogonal design. The contents of tetrahydropalmatine and total alkaloids were determined by HPLC and ultraviolet spectrophotometer, respectively. Meanwhile, the electricity consumption was determined in the extraction process. RESULTS: Comparing with conventional extraction, the microwave-assisted extraction saved time and money, and provided higher extraction yield of tetrahydropalmatine and total alkaloids. CONCLUSION: The microwave-assisted extraction has advantages in high efficiency and low cost.