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Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive nanoparticles. These results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.
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@#The surface solid dispersion of honokiol was prepared by melting method with croscarmellose sodium as carrier to improve the dissolution rate of honokiol, taking the advantage of its low melting point. The dissolution rate and stability test of surface solid dispersion of honokiol were carried out. Its physical properties were then investigated by DSC, PXRD and SEM analysis. The results indicated that the dissolution rate of honokiol from sodium solid dispersion was more than 90% at 15 min while its mean dissolution time was significantly decreased. Honokiol was distributed on the surface of croscarmellose sodium in the form of microcrystal; moreover, its dissolution behavior didn′t change significantly after six months of stability tests. Therefore, surface solid dispersion of honokionl could be prepared by simple process. The formed solid dispersion achieved high drug loading and fast in vitro dissolution rate, which could provide a novel idea for developing solid preparations of honokiol.
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OBJECTIVE:To evaluate the stability of 12 kinds of submicro emulsion in market,and screen the test method for the stability. METHODS:12 kinds of submicro emulsion in market were selected,high pressure sterilization (121 ℃,30 min), high speed centrifugation(4000 r/min,15 min),accelerated test [placing 6 months under temperature of(40±2)℃,relative hu-midity of (75 ± 5)%] were conducted to investigate the pH,particle size and other indexes,and SPSS 22.0 was used to analyze the distribution variance and chi-square test,and investigate the correlation of 3 evaluation methods. RESULTS:In terms of stabili-ty investigation,the pH value of 12 kinds of submicro emulsion decreased to some extent after accelerated test,average particle size of 6 kinds of submicro emulsion samples were greater than 300 nm,the variance of the particle size distribution of 9 kinds ap-peared in 0.05-0.15,the chi-square test results of 8 kinds distributed below 1. The average particle size of 4 kinds of submicro emul-sions changed more than 10 nm after accelerated test. In terms of stability test method,Pearson chi-square progressive significance of high pressure sterilization and accelerated test was 0.665,which was higher than 0.05,indicating there was no correlation (no significance),the stability results of high pressure sterilization can not represent the results of accelerated test;that of high speed centrifugation and accelerated test was 0.004,which was lower than 0.05,indicating stability results between high speed centrifuga-tion and accelerated test results were significantly correlated. CONCLUSIONS:The submicro emulsion in market can meet the re-quirements of stability. To a certain extent,high speed centrifugation can replace the acceleration test.
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OBJECTIVE:To establish a method for the separation and detection of related substances in baicalein,identify its structure and preliminarily explore the degradation mechanism. METHODS:HPLC was adopted to detect the baicalein,related impurities and forced destruction of degradation products in synthesis process:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid-methanol-acetonitrile(gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,the column temperature was 10℃,and the injection volume was 10μL. LC-MS/MS was conducted to identify the related substances and conjecture degradation mechanism:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid- methanol (gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,column temperature was 10℃,and the injection volume was 10μL;ion source was electrospray ion source,positive and negative ions,nebulizer pressure was 55 psi and the drying gas flow was 11 L/min,drying gas temperature was 350℃,capillary voltage was 4.0 kV,detection modes were full-scan first-order MS and selective ion full-scan second-order MS,scan ranges were m/z 100-1000 (first-order MS) and 50-500(second-order MS),ionization voltage was 80-135 eV,and the collision energy was 10-30 eV. RESULTS:The linear range of baicalein was 2.4-480μg/mL(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 2.0%;the limit of quantitation was 7.2 ng,the limit of detection was 2.4 ng. Baicalein was well separated with related substance and 3 major degradation products,the related substance was chemical synthesis precursor wood butterfly;the degradation products were 6,7-quinone derivatives and 7,8-quinone derivatives,which were isomers;oxidative degradation products were benzoic acid phenyl ester derivatives. CONCLUSIONS:The main mechanisms of alkali degradation and oxidative degradation of baicalein include pyran, reciprocal rearrangement and oxidation reaction;the established method is specific and sensitive,and can be used for the detection of related substances in baicalein.
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Injectable lipid emulsions have been routinely used in patients since 1960s as a nutritional supplement for patients requiring parenteral nutrition. In recent years, lipid injectable emulsions have been extensively studied as a kind of novel drug carrier, also the quality problems of the lipid emulsion attract more and more attentions gradually. Large diameter tail of injectable lipid emulsions as a significant quality control indicator should pay more attention. Regarding to the defect of detecting large diameter tail of lipid injectable emulsions in our country, the purpose of this article is to summarize the techniques of detecting large diameter tail, illustrate the impacts of large lipid droplet on the quality of lipid injectable emulsions, emphasize the importance of detecting large diameter tail in lipid emulsions and provide guidance for researching and developing lipid emulsions in domestic market.
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Bicyclol with benzyl alcohol structure, is a poorly water-soluble drug, used for the treatment of chronic hepatitis B. To increase the drug solubility and oral bioavailability, a Bicyclol-phospholipid complex was studied on its preparation, formation mechanism, and the influence on drug physicochemical properties and oral absorption. The complex was prepared by a solvent evaporation method. The optimal formulation was selected by orthogonal experimental design, and a reasonable evaluating method of the complexation rate was established. Various methods, such as differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and 31P nuclear magnetic resonance (31P-NMR), were used to explore the phase state and formation mechanism of the complex. The solubility of drug in complex was investigated in water/n-octanol. Preliminary study of its absorption and liver tissue distribution in rats was also carried out. The results showed that Bicyclol and phosphatidylcholine can be complexed entirely in the molar ratio 1 : 2. Bicyclol was dispersed in phospholipids as amorphous state. They were combined by intermolecular hydrogen bond due to charge transfer effect which occurred between the two polarities of the double bond between phosphorus and oxygen (P=O) of phosphatidylcholine and benzalcohol group of Bicyclol. The solubility of the complex compared to the active pharmaceutical ingredient (API) was effectively enhanced 5.75 times in water and 7.72 times in n-octanol, separately. In addition, drug concentrations were also enhanced 43 times in plasma and 13 times in liver with one hour after administering the complex to rats via oral gavage. All of these indicated that Bicyclol with benzalcohol group can interact with phospholipids to form complex, improving drug's physicochemical properties, thus further increasing its absorption and target tissue distribution. This study also provided theoretical reference for the research of other benzalcohol derivatives complexed with phospholipids.