In the present study, liquiritigenin-phospholipid complex (LPC) was developed and evaluated to increase the oral bioavailability of liquiritigenin. A single-factor test methodology was applied to optimize the formulation and process for preparing LPC. The effects of solvent, drug concentration, reaction time, temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated. LPCs were characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD). The apparent solubility and n-octanol/water partition coefficient were tested. The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone. An LPC was successfully prepared. The optimum level of various parameters for liquiritigenin-phospholipid complex was obtained at the drug concentration of 8 mg·mL
Administration, Oral ; Animals ; Biological Availability ; Flavanones/pharmacokinetics* ; Phospholipids/pharmacokinetics* ; Rats ; Solvents

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.
1-Octanol ; Animals ; Biological Availability ; Biphenyl Compounds ; pharmacokinetics ; Calorimetry, Differential Scanning ; Chemistry, Pharmaceutical ; Phospholipids ; pharmacokinetics ; Rats ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Tissue Distribution ; X-Ray Diffraction

AIMTo prepare silybin-phospholipid complex and study its physicochemical properties. To compare the pharmacokinetic characteristics and bioavailability after oral administration of silybinphospholipid complex and silybin material in rats.

METHODSUsing acetone as a reaction medium, silybin and phospholipid were resolved into the medium, when the organic solvent was clear, then removed under vacuum evaporation, silybin-phospholipid complex was obtained. The new complex' s physicochemical properties including DSC, UV, IR were determined. The concentrations of non-conjugated and total silybin after oral administration of silybin-phospholipid complex and silybin material at different time in rats were determined by RP-HPLC. The pharmacokinetic parameters were computed by software program 3P97.

RESULTSExperiment results showed that silybin and phospholipid in the silybin-phospholipid complex were combined by non-covalent-bond, not forming a new compound and the solubility of silybin-phospholipid complex in water and n-octanol was effectively enhanced. It was found that mean plasma concentration-time curve of silybin after oral administration of silybin-phospholipid complex in rats was in accordance with one-compartment model with first-order absorption. Pharmacokinetic parameters of non-conjugated and total silybin in rats were respectively T(max) 10 min and 2 h; C(max) 0.11 and 1.08 microg x mL(-1); T1/2 2.18 and 3.84 h; AUC(0-infinity) 1.71 and 12.94 microg x mL(-1) x h. However, after oral administration of silybin material, plasma levels of both non-conjugated and total silybin were within the analytical detection limit.

CONCLUSIONIt was concluded that after oral administration of silybin-phospholipid complex in rats the bioavailability of silybin increased greatly. This was mainly due to an obvious improvement of the lipophilic property of silybin-phospholipid complex compared with silybin material and an increase in gastrointestinal absorption.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Drug Compounding ; Male ; Phospholipids ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Silymarin ; administration & dosage ; blood ; pharmacokinetics ; Solubility

OBJECTIVETo study the plasma concentration-time curve, pharmacokinetic parameters and bioavilability of oxymatrine-phospholipid complex and to compare with oxymatrine in rats.

METHODRats were given oxymatrine-phospholipid 100 mg x kg(-1). Blood samples were collected at different times after oral administration. The internal standard was cimetidine. Protein in plasma was precipitated with merhanol and centrifuged at high speed. The supernatant was directly injected and assayed by CE method. The running buffer was 0.04 mol x L(-1) Tris-10 mmol x L(-1) sodium phosphate monobasic-40% isopropanol pH to 7.6 with phosphoric acid. The wavelength of detection was 205 nm.

RESULTThe AUC of oxymatrine and oxymatrine-phospholipid complex were 4.52 mg x mL(-1) x h(-1) and 6.21 mg x mL(-1) x h(-1), respectively. The oxymatrine-phospholipid bioavailability enhanced 1.4 times.

CONCLUSIONIt is concluded that after oral administration of oxymatrine-phospholipid complex in rats the bioavailability of oxymatrine is increased greatly. This is mainly due to an obvious improvement of the lipophilic property of oxymatrine-phospholipid complex compared with oxymatrine material and an increase in gastrointestinal absorption.

Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; chemistry ; pharmacokinetics ; Area Under Curve ; Biological Availability ; Male ; Phospholipids ; chemistry ; Plants, Medicinal ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Sophora ; chemistry

OBJECTIVETo optimize the formulation and preparation process of sinomenine liposomes.

METHODMethod of aether injection and mixture uniform design were adopted to determine the formulation of sinomenine liposomes is the proportion of phospholipids, cholesterol and Vitamin E with the index of entrapment efficiency. And the single-factor test was used to study the preparation process of the liposomes, including the volume of buffer solution, the preparation temperature and the ultrasonic time.

RESULTThe optimized formulation was that the ratio of sinomenine : phospholipids : cholesterol : vitamin E mass ratio was 8.92 : 60.35 : 28.81 : 1.91. The volume of buffer solution was 50 mL x g(-1) membrane, the preparation temperature was 50 degrees C, and the ultrasonic time was 20 min.

CONCLUSIONSatisfactory shape and entrapment efficiency of the liposomes can be obtained by the optimized formulation and preparation process.

Chemistry, Pharmaceutical ; Cholesterol ; Dosage Forms ; Drug Carriers ; Drug Compounding ; economics ; methods ; Drug Delivery Systems ; Drug Stability ; Liposomes ; Morphinans ; pharmacokinetics ; Particle Size ; Phospholipids ; Technology, Pharmaceutical

To investigate the absorption kinetics of Cu B-SDC/PLC-MMs in rat different intestinal segments and compared with the absorption of Cu B suspension. The in vitro everted gut sacs model was established to study the absorption characteristics of Cu B-SDC/ PLC-MMs in rat duodenum, jejunum, ileum and colon, and the content of cucurbitacin B was detected by HPLC method, and the effects of concentrations on intestinal absorption were evaluated as well. The results showed that the absorption of Cu B-SDC/PLC-MMs was linearity at different intestine segment and different concentrations (R2 > 0.9), which was consistent with zero order rate process. The Ka of different intestine segments showed a concentration-dependent increasing along with the raised concentration of Cu B-SDC/ PLC-MMs, indicating that it was likely to be a mechanism of passive absorption. The best absorption site of Cu B-SDC/PLC-MMs was ileum, and its absorptions in different intestinal segments were superior to cucurbitacin B suspension. SDC/PLC-MMs could significantly enhance the intestinal absorption of cucurbitacin B, and the study of intestinal absorption kinetics of Cu B-SDC/PLC-MMs had gave a support to its further reasonable solidfication.
Animals ; Deoxycholic Acid ; administration & dosage ; Female ; Intestinal Absorption ; Kinetics ; Male ; Micelles ; Nanoparticles ; Phospholipids ; administration & dosage ; Rats ; Rats, Wistar ; Triterpenes ; administration & dosage ; pharmacokinetics

OBJECTIVETo investigate whether the absorption of breviscapine can be enhanced by using breviscapine photosomes.

METHODTesting the uptake and intestinal permeability of breviscapine powder and breviscapine photosomes by using intestine perfusion technique and reverted gut sac method.

RESULTThe uptake and permeability coefficient of breviscapine were increased in photosomes. The absorption process obeyed the Fick's law in the range of 0-100 microg x mL(-1).

CONCLUSIONThe absorption breviscapine photosomes is enhanced by increasing the permeability through a passive mechanism.

Animals ; Asteraceae ; chemistry ; Drug Carriers ; Flavonoids ; administration & dosage ; isolation & purification ; pharmacokinetics ; Intestinal Absorption ; Intestine, Small ; metabolism ; Male ; Phospholipids ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo prepare silybin lipid nanospheres (SLN) and to evaluate the properties of morphology, particle size and the silybin distribution in mice.

METHODSilybin lipid nanospheres were prepared by thin film emulsion-high pressure homogenization technique. Concentrations of silybin in mice blood, liver, spleen, lung, kidney, brain, heart, stomach after oral administration were determined by high performance liquid chromatography.

RESULTScanning electron micrograph showed that most of the SLN were spherical. The average diameter from photon correlation spectrometer was 148.9 nm with the polydispersity 0.17. Body distribution data indicated that SLN could increase the distribution of silybin in blood and liver, decrease the amount of silybin in stomach as compared with the preparation on market, and the drug targeting index (DTI) in liver was 1.81.

CONCLUSIONSLN can increase the uptake of silybin in liver after oral administration, which must benefit the hepatitis treatment.

Administration, Oral ; Animals ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Liver ; metabolism ; Mice ; Nanoparticles ; Particle Size ; Phospholipids ; Random Allocation ; Silymarin ; administration & dosage ; pharmacokinetics ; Tissue Distribution

AIM: To improve the absorption of thymopeptides (TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs). METHODS: TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties. RESULTS: A narrow size distribution of nanomicelles, with a mean particle size of (149 ± 8.32) nm and a zeta potential of (-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice. CONCLUSIONS TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.
Animals ; Chemistry, Pharmaceutical ; Deoxycholic Acid ; chemistry ; Drug Carriers ; chemistry ; Drug Stability ; Mice ; Micelles ; Particle Size ; Peptides ; administration & dosage ; chemistry ; pharmacokinetics ; Phospholipids ; chemistry ; Rats ; Rats, Wistar ; Thymus Gland ; chemistry

To increase drug concentration in the head through intranasal administration, we have investigated the excised animal nasal mucosa permeability and nasal toxicity of the baicalin drug carrier systems, such as baicalin liposomes, beta-cyclodextrin inclusion compound, and phospholipid complex. A transport of baicalin drug carrier systems through nasal mucosa was simulated in diffusion chamber in vitro, and swine, caprine and rabbit nasal mucosa was used, the concentration of drug in the receptor was determined by HPLC. By taking the apparent permeability coefficients as evaluation standard, investigated the isolated animal nasal mucosa permeability of different baicalin drug systems was investigated for screening the best baicalin drug carrier system through nasal cavity administration. Toxicity of baicalin and its phospholipids complex on toad palate mucosal cilia movement and rats nasal mucosa long-term toxicity were studied in vivo. The apparent permeability coefficient of three kinds of baicalin drug carrier systems was better than that of baicalin (P < 0.05), and its lag-time was obviously shortened. At the same time, the apparent permeability coefficient of phospholipid complex was higher than those of other two drug carrier systems (P < 0.05). The results showed that the baicalin phospholipids complex nasal mucosa permeability was obviously superior to the other two drug systems. Baicalin phospholipids complex had no toxicity to ciliary movement, and had no irritation to rat nasal mucosa. The results show that baicalin phospholipid complex was the best baicalin drug carrier system, it could significantly enhance the permeability of baicalin across nasal mucosa, had no toxicity to nasal mucosa, and could be used for intranasal administration.
Administration, Intranasal ; Animals ; Bufo bufo ; Drug Carriers ; pharmacokinetics ; toxicity ; Drug Delivery Systems ; Female ; Flavonoids ; administration & dosage ; pharmacokinetics ; toxicity ; Goats ; Liposomes ; pharmacokinetics ; toxicity ; Male ; Nasal Mucosa ; drug effects ; metabolism ; Palate ; drug effects ; Permeability ; Phospholipids ; pharmacokinetics ; toxicity ; Rabbits ; Random Allocation ; Rats ; Swine ; beta-Cyclodextrins ; pharmacokinetics ; toxicity