Formulation development and pharmacokinetics of puerarin self-emulsifying drug delivery systems.

The main purpose of this work was to prepare a self-emulsifying drug delivery system (SEDDS) for a poorly water-soluble drug, puerarin. The solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided relatively higher solubility. The addition of propylene glycol as a cosurfactant improved the solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures composed of oleic acid, propylene glycol, and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region, and the particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations were investigated in beagle dogs. The bioavailability of puerarin was compared using the pharmacokinetic parameters, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and total area under the plasma concentration-time curve (AUC(0-infinity)). The analysis of the data showed a statistically significant difference between F2 and F4 (P < 0.01) as well as F3 and F4 (P < 0.01) with regard to the values of AUC(0-infinity) and C(max) but not between those of F2 and F3 (P > 0.05). In the case of parameter T(max), ke, no statistically significant difference (P > 0.05) among the values were observed. From these studies, a SEDDS containing oleic acid (17.5%), Tween 80 (34.5%), and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation for puerarin. The data suggest the potential use of SEDDS to improve the oral absorption of puerarin.

Synthesis of hydrogel polymer coated ZnO nanoparticles and their decontaminating effect against soman in vitro / 中国药理学与毒理学杂志

OBJECTIVE To evaluate the decontamination capability of hydrogel polymer coated ZnO nanoparticles (ZnO NP-gel) against soman. METHODS ZnO NP was synthetized using chemical precipitation method and modified with 4-pentenoic acid,and then polymerized with comonomers to obtain ZnO NP-gel. The transmission electron microscope (TEM), scanning electron microscope (SEM) and particle size instrument were used to observe the internal structure,micromorphology,particle size and zeta potential of these materials. An infrared spectroscope (IR) was used to analyze their chemical bond structure,while X-ray diffraction (XRD) was used to analyze the diffraction pattern.The content of soman was determined by benzidine chromogenic reaction. ZnO NP(1 g·L-1), ZnO NP-gel (1 g·L-1) and distilled water were mixed with soman(52.2 mg·L-1),stood for 30 min,and then filtered before filtrate was subcutaneously injected into mice (40 μL·g-1) to observe the symptoms of poisoning and death. RESULTS SEM and TEM showed that ZnO NP-gel had a block structure, the zeta potential of which was (-7.89 ± 0.04) mV. The results of IR indlicated that ZnO NP-gel had stronger absorption peaks at 754 and 618 cm-1, and XRD revealed that these materials had a sharp peak at 2θ=8.06738°. The decontamination efficiency of ZnO NP-gel was higher than that of ZnO NP group at the same concen?tration (n=3, P<0.05), and the time for decontamination of 50% soman was shortened by four times. The mice were injected subcutaneously with the soman solution treated with ZnO NP-gel, which caused no convulsion or death. CONCLUSION ZnO NP-gel can perform the double function of fast adsorption and catalysis of soman,and the decontamination ability of which could be improved through polymer modification.

Characterization of taste-masking dry emulsion of azithromycin by in vitro and in vivo evaluation / 药学学报

To develop a taste-masking oral preparation of azithromycin for pediatrics, the reversed lipid nano-micelle techniques were used to mask the bitterness of azithromycin. Dry emulsion (DE) for taste-masking was prepared by solidifying the reversed-micelle oil solution containing azithromycin. Colloidal silicon dioxide was used as absorbent and solid carrier. Solidification was confirmed through dying test and observed by scanning electron microscope (SEM). The DE formulation was characterized by X-ray powder diffraction and SEM in order to investigate the crystal state of drug. Reconstitution emulsion droplet size and morphology were also determined using Nano ZS90 Zetasizer and transmission electron microscopy (TEM). The taste testing was performed in two different ways, namely, human taste panel test and the measurement of the amount of drug released in simulated oral cavity condition. The intestinal mucosal irritation test of DE formulation was also investigated in rats in comparison with commercial product (Zithromax). The optimal taste-masking formulation of azithromycin can be re-dispersed immediately with mean diameter of 530.1 nm after agitation in water. The results of taste testing showed that the bitterness of azithromycin was successfully masked by DE formulation similar with Zithromax at the same dose, moreover reduced intestinal irritation compared to Zithromax. These results indicate that the DE formulation for taste-masking of azithromycin is promising and valuable in the future development of azithromycin for pediatrics.

Rheological properties of poloxamer 407 aqueous solutions / 药学学报

Rheological properties of poloxamer 407 (brand named Pluronic F127) were examined by changing shear rate, temperature and the recovery properties of apparent viscosity after heating for several times. The results indicated that poloxamer 407 aqueous solution showed a Newtonian behavior at a low concentration while it might be a pseudoplastic fluid when the concentration reached a certain point. The thixotropy and the sol-gel transition temperature decreased with increasing the concentration (it could be an in situ gel at body temperature when the concentration of poloxamer 407 up to 15.25%). The results that obtained from the theological data would be useful in the application of poloxamer 407 such as in situ gel preparation.

Multivesicular liposome sustained delivery of a novel synthetic electropositive Positive GnRH antagonist LXT-101: preparation and in vitro evaluation / 药学学报

Using a simple method to determine the interaction between peptide and lipid bilayer and then deciding how to modify formulation from classic DepoFoam technology, multivesicular liposome of LXT-101 (DepoLXT-101) was prepared and characterized by in vitro evaluation. The electrostatic adsorption between peptide and lipid bilayer was observed by zeta potential and fluorescence spectrum. Anionic surfactants were added to stable the multiple emulsion and minimize the opposite effects resulted from drug. Encapsulation efficiency was determined by RP-HPLC. Morphology, particle size of DepoLXT-101 particles were characterized and their in vitro release was studied in sodium chloride solution. The DepoLXT-101 particles were prepared with good encapsulation efficiency, narrow size distribution and multivesicular construction. Over 95% of the DepoLXT-101 particles were in a size range of 5-20 microm. The in vitro assay in sodium chloride solution at 37 degrees C showed that 70%-90% of the peptide was released from particles slowly over 11 days. Multivesicular liposome sustained delivery of synthetic cationic peptides could be successfully prepared by the method.

Formulation optimization of self-emulsifying preparations of puerarin through self-emulsifying performances evaluation in vitro and pharmacokinetic studies in vivo / 药学学报

The main purpose of this work is to prepare self-emulsifying drug delivery system (SEDDS) of a poorly water soluble drug, puerarin. Solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided higher solubility. Addition of propylene glycol as cosurfactant improved solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures comprising oleic acid, propylene glycol and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The pharmacokinetic behaviors of three different SEDDS formulations (F2, F3, F4) were investigated in Beagle dogs. The bioavailability was compared using the pharmacokinetic parameters, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)) and total area under the plasma concentration-time curve (AUC(0-t)). AUC(0-t) was significantly higher in formulation F2 group (5.201 +/- 0.511) ng x mL(-1) x h and formulation F3 group (5.174 +/- 0.498) ng x mL (-1) x h than that in formulation F4 group (3.013 +/- 0.623) ng x mL(-1) x h. Also, C(max) was significantly higher in formulation F2 group (1.524 +/- 0.125) ng x mL(-1) and formulation F3 group (1.513 +/- 0.157) ng x mL(-1) than that in formulation F4 group (0.939 +/- 0.089) ng x mL(-1). Further analysis of the data showed a statistically significant difference between F2 and F4 (P < 0.01) as well as F3 and F4 (P < 0.01) with regard to the values of AUC(0-infinity) and C(max) for three SEDDS formulations, but not between those of F2 and F3 (P > 0.05). From these studies, the SEDDS formulation containing oleic acid (17.5%), Tween 80 (34.5%) and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation of puerarin. The data suggest the potential use of SEDDS to improve oral absorption of puerarin.

Assesement of tretinoin with a self-emulsifying formulation in vitro and in vivo / 药学学报

<p><b>AIM</b>To evaluate the self-emulsifying ability and dissolution behavior of tretinoin in vitro and the pharmacokinetic behavior in beagle dogs.</p><p><b>METHODS</b>The self-emulsifying rate was evaluated by determining the intensity of scattered light at different time and the particle size of resultant emulsions after self-emulsifying were observed by optical microscope. The plasma concentrations were determined by HPLC and dissolution and pharmacokinetic behavior of self-emulsifying formulations were evaluated by comparison with commercial capsules.</p><p><b>RESULTS</b>The area under the curve (AUC) was significantly higher in the tretinoin self-emulsifying formulation group (3048.0 mg x h x L(-1)) than that in the commercial capsule group (1826.0 mg x h x L(-1)). Also, Tmax was smaller in the self-emulsifying formulation group (1.25 h) compared with market products (2 h) and the dissolved amount from self-emulsifying formulations in water at 15 min was much higher (more than 80%) than that of the market products (less than 5%).</p><p><b>CONCLUSION</b>The self-emulsifying drug delivery systems can increase drug dissolution in vitro and absorption in vivo significantly.</p>

Studies on quality control of dexamethasone liposomes / 药学实践杂志

OBJECTIVE：To study the main aspects of quality control of dexamethasone liposomes.METHODS:The structure of liposomes was studied with negative staining method of TEM.K-ratio spectrophotometry was wsed to determine the contert,and the Macrosep was wsed to seperate the entrapped from free drugs.RESULTS:An excellent linear relationship was obtained with the range of 4～52μg/ml,the average recovery percent was between 98.28%～99.71%.The entrapment efficiency was one of the important parameters of liposomes quality control.It was related with the clinical effect directly,the entrapment efficiency was more than 80%.CONCLUSION:This method is accurate,quick and reproducible.