Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals.

Many phytochemicals show promise in cancer prevention and treatment, but their low aqueous solubility, poor stability, unfavorable bioavailability, and low target specificity make administering them at therapeutic doses unrealistic. This is particularly true for (-)-epigallocatechin gallate, curcumin, quercetin, resveratrol, and genistein. There is an increasing interest in developing novel delivery strategies for these natural products. Liposomes, micelles, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and poly (lactide-co-glycolide) nanoparticles are biocompatible and biodegradable nanoparticles. Those nanoparticles can increase the stability and solubility of phytochemicals, exhibit a sustained release property, enhance their absorption and bioavailability, protect them from premature enzymatic degradation or metabolism, prolong their circulation time, improve their target specificity to cancer cells or tumors via passive or targeted delivery, lower toxicity or side-effects to normal cells or tissues through preventing them from prematurely interacting with the biological environment, and enhance anti-cancer activities. Nanotechnology opens a door for developing phytochemical-loaded nanoparticles for prevention and treatment of cancer.

Novel ophthalmic timolol meleate liposomal-hydrogel and its improved local glaucomatous therapeutic effect in vivo.

To overcome the limitations of common eye drops, the study developed a novel timolol mealate (TM) liposomal-hydrogel to enhance drug permeability and prolong residence time in the precorneal region, which achieved more effective local glaucomatous therapeutic effect. Firstly, TM liposome was prepared by an ammonium sulfate gradient-pH regulation method, which its entrapment efficiency reached up to 94% and its averaged particle size is 187 nm with narrow distribution. The corneal permeability through isolated rabbit cornea was measured by modified Franz-type diffusion cells. The results of trans-corneal penetration exhibited that the apparent permeability coefficients (P(app)) and the flow rates of steady state (J(ss)) of TM liposome was 1.50-fold higher than that of the commercialized eye drop, while TM liposome with 0.02% transcutol P was 2.19 times. In order to increase the retention time and improve the stability of liposome, we further developed a TM liposomal-hydrogel formulation by adding 1.0% HPMC K4M in TM liposome. The results showed an stability during a 120 days storage period than TM liposome. Precorneal retention study in vivo indicated that the optimal liposomal-hydrogel formulation had improved bioavailability and its retention time on rabbit corneal surface were significantly longer than that of pure liposomes or eye-drops. No obvious irritations to rabbit eyes were observed by histopathology microscopy after 7 days exposure.. Comparing to the eye drops, the TM liposomal-gel displayed prolonged therapeutic effect in cornea and greatly lowered the intraocular pressure IOP on the eyes of normal and glaucomatous pigmented rabbits.

[Comparison of the characteristics of several polymer materials used in hydrophilic matrix tablets].

Pure and drug hydrophilic matrix tablets were prepared by direct compression method with theophylline as a model drug. The characteristics of four hydrophilic matrix polymers, hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), sodium alginate (NaAlg) and xanthan gum (XG), were compared by investigating the water absorption, swelling, erosion and gel layer strength. The sequence of water absorption rate was XG >> NaAlg (H) > PEO > NaAlg (L) >> HPMC; The sequence of swelling index was XG >> PEO >> HPMC >> NaAlg; The sequence of erosion rate was NaAlg (L) > NaAlg (H) >> PEO80 > PEO200 > PEO300 > XG approximately PEO400 approximately K4M > K15M > PEO600 approximately K100M; The sequence of the gel layer strength was PEO > HPMC > XG >> NaAlg. For the PEO and HPMC matrix tablets, with the polymer molecular weight increased, the drug release mechanism was gradually transferred from mainly depending on the erosion to the diffusion; for SAL matrix tablets, the drug release mainly depends on erosion mechanism; and for XG matrix tablets, the drug release mainly depends on non-Fick diffusion mechanism. Comparison of the performance difference between the polymer materials will contribute to rational design and prediction of drug release behaviors from matrix tables and ultimately to achieve clinical needs.

A novel paclitaxel microemulsion containing a reduced amount of Cremophor EL: pharmacokinetics, biodistribution, and in vivo antitumor efficacy and safety.

The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution, in vivo antitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P < .01). In conclusion, the PTX microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy.

[Optimization of a floating osmotic pump system of dipyridamole using central composite design-response surface methodology].

A new type of floating osmotic pump of dipyridamole was designed in this paper. Apparatus three (Chinese Pharmacopeia 2005, appendix XD) was employed for in vitro dissolution test in order to evaluate the release and floating behavior in a same experiment. The system was optimized using central composite design-response surface methodology; where similarity factor (f2) between the dissolution profile of prepared formulation and the target dissolution profile was taken as dependent factor, usage amount of polyoxyethylene (X1, mg), NaCl (X2, mg) and pore former (PEG4000, X3, %) were taken as independent factors. The optimization model was f2 = -29.3 + 2.35X3 - 0.123X1(2) - 0.046X2(2) + 0.145X1X2 (R = 0.996). It was found that the dissolution profile could match the target dissolution profile under the condition of weight gain 8%-9%, X1 (20-34), X2 (30-57), X3 = 50. It is also found that the minimum usage percentage of pore former is 35.1%. The prediction results of the optimization model were good in the experiments.

Overcome side identification in PPOP by making orifices on both layers.

The original purpose of this research was to build a database for an expert system. Unexpectedly, it was found that the color-identifying device in push-pull osmotic pump (PPOP) manufacturing process could be unnecessary. Water-insoluble drug indapamide, gliclazide and dipyridamole were employed as model drugs. Bunches of conventional formulations were designed; and traditional preparation procedures were used. In vitro drug release was studied; and the similarity between the conditions of orifice only on the side of the drug layer and orifices of the same diameter on both sides was evaluated. It was found that the drug release from PPOP could be influenced by formulation and core hardness while it could hardly be influenced by orifice size. No significant difference was observed between the dissolution profiles of orifice only on the side of the drug layer and orifices of the same diameter on both sides. Mechanism of drug release was discussed. The conclusion was that the disadvantage of side identification in PPOP manufacturing process could be overcome by drilling orifices on both sides.

Preparation and evaluation of self-microemulsifying drug delivery system containing vinpocetine.

The main purpose of current investigation is to prepare a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of vinpocetine, a poorly water-soluble drug. Suitable vehicles were screened by determining the solubility of vinpocetine in them. Certain surfactants were selected according to their emulsifying ability with different oils. Ternary phase diagrams were used to identify the efficient self-microemulsifying region and to screen the effect of surfactant/cosurfactant ratio (K(m)). The optimized formulation for in vitro dissolution and bioavailability assessment was oil (ethyl oleate, 15%), surfactant (Solutol HS 15, 50%), and cosurfactant (Transcutol P, 35%). The release rate of vinpocetine from SMEDDS was significantly higher than that of the commercial tablet. Pharmacokinetics and bioavailability of SMEDDS were evaluated. It was found that the oral bioavailability of vinpocetine of SMEDDS was 1.72-fold higher as compared with that of the commercial tablet. These results obtained demonstrated that vinpocetine absorption was enhanced significantly by employing SMEDDS. Therefore, SMEDDS might provide an efficient way of improving oral bioavailability of poorly water-soluble drugs.

A controlled-release ocular delivery system for ibuprofen based on nanostructured lipid carriers.

The objective of this study was to develop an ocular drug delivery system based on nanostructured lipid carrier and investigate its in vitro and in vivo characteristics. Ibuprofen was chosen as the model drug. Four different formulations of ibuprofen nanostructured lipid carriers were prepared by melted-ultrasonic methods; gelucire 44/14 was screened as one of the solid lipid matrix materials due to the good particle size dispersion and excellent contribution to the corneal permeability of the model drug. The modified Franz-type diffusion cells and isolated corneas were used in the test of drug corneal permeability and the in vivo releasing tests were carried out using microdialysis method. gelucire 44/14 and transcutol P could enhance the corneal permeability by different mechanisms. The corresponding apparent permeability coefficients (P(app)) were 1.28 and 1.36 times more than that of the control preparation. Stearylamine could prolong the pre-cornea retention time of the model drug to some extent. Ibuprofen nanostructured lipid carriers displayed controlled-release property. The AUC of the optimized formulation of ibuprofen nanostuctured lipid carriers was 3.99 times more than that of ibuprofen eye drops).

[Design and in vitro evaluation of self-microemulsifying drug delivery systems for piroxicam].

Self-microemulsifying drug delivery systems (SMEDDS) were developed to overcome the problems of delivery and administration of piroxicam, a drug with low bioavailability and gastrointestinal irritation, The in vitro properties of it were assessed. The solubility of piroxicam in several oils and surfactants was determined, and the compatibility of various oils and surfactants was investigated. Ternary phase diagrams were constructed to optimal area of microemulsion, and the influence of different oily phases, surfactants and co-surfactants was studied. The droplet size and dissolution of optimal formulation were determined to prove that the dosage form is a useful delivery system for piroxicam. In the optimized piroxicam SMEDDS, cinnamic alcohol was selected that gave the maximal solubility to piroxicam. Labrafil M 1944CS, Cremophor EL and Transcotol P were used as oils, surfactant and co-surfactant, respectively. Droplet size and distribution of three piroxicam SMEDDS formulations were (32.2 +/- 5.0), (40.1 +/- 6.4), (81.9 +/- 12.2) nm individually. And the releasing of piroxicam was rapid and complete. The optimized SMEDDS for piroxicam was obtained.

A novel time-controlled release system based on drug-resin complexes and elementary osmotic pump.

A novel time-controlled system based on elementary osmotic pump tablet containing a drug-resin complexes (DRCs) core is presented. In the traditional osmotic pump tablets (OPTs), the lag time was always minimized. On the contrary, in the DRCs osmotic pump tablet (DRCOPT), the lag time was increased to achieve time-controlled delivery. The system led to a zero-order drug release after an initial lag time. Polyethylene oxide (PEO) N80 was used as suspension agent and NaCl was applied as ion-exchange, osmotic pressure (electrolyte supplementary) agent, respectively. To examine the mechanism of this system, drug release behaviors were investigated under conditions of various osmotic pressures. A new method of combination of conductivity and HPLC was applied to determine the different fractions of NaCl in producing osmotic pressure, ion-exchange and electrolyte supplement. The pharmacokinetic studies conducted in beagle dogs showed that a steadier and controlled drug release behavior was obtained compared with the traditional formulations. On the basis of prescription of the DRCOPT, a good in-vitro-in-vivo correlation (IVIVC, R(2)=0.9541) was achieved. In addition, a lag time of 4 h was observed in in vivo experiment, which indicated that the DRCOPT can be used in therapeutic regimens with the characteristics of chronotherapy.

Temperature-responsive, Pluronic-g-poly(acrylic acid) copolymers in situ gels for ophthalmic drug delivery: rheology, in vitro drug release, and in vivo resident property.

To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic-g-poly(acrylic acid) copolymers were studied as a temperature-responsive in situ gelling vehicle for an ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels, as well as the in vivo resident properties of such in situ gel ophthalmic formulations, were investigated. The rheogram and in vitro drug release studies indicated that the drug release rates decreased as acrylic acid/Pluronic molar ratio and copolymer solution concentration increased. It was also shown that the drug concentration had no obvious effect on drug release. The release rates of drug from such copolymer gels were mainly dependent on the gel dissolution. In vivo resident experiments showed the drug resident time and the total resident amount increased by 4-fold and 1.2-fold for in situ gel compared with eye drops. These in vivo experimental results, along with the rheological properties and in vitro drug release studies, demonstrated that in situ gels containing Pluronic-g-PAA copolymer may significantly prolong the drug resident time and thus improve bioavailability. The results showed that the Pluronic-g-PAA copolymer can be a promising in situ gelling vehicle for ophthalmic drug delivery.

[Preparation of PEG-modified nanostructured lipid carriers loaded with hydroxycamptothecin and tissue distribution in mice].

Hydroxycamptothecin (HCPT) loaded PEG modified nanostructured lipid carriers (HCPT-PEG-NLC) and nanostructured lipid carriers (HCPT-NLC) were prepared by melt emulsification and homogenization method. The morphology, particle size and encapsulation efficiency of them were investigated. HCPT concentrations in plasma, heart, liver, spleen, lung, kidney and ovary were determined after iv of HCPT injection, HCPT-PEG-NLC and HCPT-NLC in mice. The targeting indexes of HCPT-PEG-NLC and HCPT-NLC were calculated. The transmission electron microscope imaging showed that HCPT-PEG-NLC and HCPT-NLC exhibited a spherical shape. The particle sizes of them were (88.6 +/- 22.5) and (127.2 +/- 43.4) nm. The encapsulation efficiency were (90.51 +/- 3.29)% and (84.37 +/- 2.81)%, respectively. After iv injection into the tail vein of mice, HCPT plasma concentrations of HCPT-PEG-NLC and HCPT-NLC were higher than that of HCPT injection at each sampling time. They also showed longer elimination time in every tissue. HCPT-NLC accumulated in endothelial system (RES), Re and Ce of it in liver and spleen were significantly higher than HCPT-PEG-NLC. HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT. MRT and AUC0-24 h of it were 19.80 and 17.02 times higher than those of HCPT injection. It also significantly reduced phagocytosis of RES, and showed lung targeting effect (Re and Ce were 14.51 and 41.35). To summarize, HCPT-PEG-NLC could prolong the circulation time of HCPT in vivo, and had the lung targeting effect. It was a promising carrier to increase therapeutic effect of HCPT in treating lung cancer.

[Tissue distribution of solid lipid nanoparticles loaded garlic oil in rats].

OBJECTIVE: To investigate the tissue distribution of the diallyl disulfide (DADS) and diallyl trisulfide (DATS) in solid lipid nanoparticles loaded garlic oil (GO-SLN) in rats. METHOD: The gas chromatography-electron capture detection (GC-ECD) method was established to determined the DADS and DATS simultaneously in the biological samples of rats after administration of 0.5 mL garlic oil injection or GO-SLN (containing about 10 mg garlic oil) via jugular vein cannula. The conditions for gas chromatographic separation were as follows. The oven temperature was set at 110 degrees C and maintained for 15 min. Temperatures at the injection port and detector were 180 degrees C and 300 degrees C, respectively. Ultra-pure nitrogen (purity > 99.999%, Shenyang Kerui Special Gases Co. Ltd., China) was used as a carrier gas and made-up gas at flow-rates of 1 mL x min(-1) and 60 mL x min(-1), respectively. All injections were carried out in the split injection mode with a split ratio of 1:10. RESULT: The GC-ECD method was fit for determing the concentration of DADS and DATS in garlic oil. The distribution character of GO-SLN in rats had changed to some extent and the concentration of GO-SLN in tissues was higher than that of GO-Injection. CONCLUSION: The SLN can elevate the passive targeting of drugs and lengthen their action time in tissues.

[Study on in vitro release empirical method and the release mechanism of budesonide colonic localization tablet].

The three-step dissolution experiment was established to investigate the in vitro release of budesonide colon-specific tablet and to elucidate the drug release mechanism by fitting to different mathematical models. The physiological parameters of stomach, small intestine and colon such as pH value, intestinal flora, specific organic enzyme, vermiculation and conveying time were mimicked to plot the in vitro dissolution, separately. Sample were taken at predetermined time intervals in 24 h and the accumulated drug releases were determined by using HPLC method. Drug release curves of the localization tablets were fitted to various mathematical models. It shows that no drug release was found in 2 h. About 5% release was determined after 6 h while 77.5% accumulated release was reached within 24 h. Drug release from the in house formulation fitted well into first-order model. The three-step dissolution method could be used to evaluate the colon-specific characteristics of budesonide colonic localization tablet. The drug release behavior of the localization tablet conforms to the drug release mechanisms of controlled porosity osmotic pump where osmotic pressure is the main driving force for controlled delivery of drugs.

Pluronic F127-g-poly(acrylic acid) copolymers as in situ gelling vehicle for ophthalmic drug delivery system.

To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic F127-g-poly(acrylic acid) copolymers were studied as in situ gelling vehicle for ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels were investigated. The rheogram and in vitro drug release studies indicated that the drug release rates decreased as acrylic acid/Pluronic molar ratio and copolymer solution concentration increased. But the drug concentration had no obvious effect on drug release. The release rates of the drug from such copolymer gels were mainly dependent on the gel dissolution. In vivo resident experiments showed the drug resident time and the total resident amount in rabbit's conjunctiveal sac increased by 5.0 and 2.6 folds for in situ gel, compared with eye drops. The decreased loss angle at body temperature and prolonged precorneal resident time also indicated that the copolymer gels had bioadhesive properties. These in vivo experimental results, along with the rheological properties and in vitro drug release studies, demonstrated that in situ gels containing Pluronic-g-PAA copolymer may significantly prolong the drug resident time and thus improve bioavailability. Pluronic-g-PAA copolymer can be a promising in situ gelling vehicle for ophthalmic drug delivery system.

Application of a novel approach to prepare biodegradable polylactic-co-glycolic acid microspheres: surface liquid spraying.

A novel approach which had foreground of industrialization, surface liquid spraying, was studied in this paper to prepare biodegradable polylactic-co-glycolic acid (PLGA) microspheres for controlled release drug delivery system. To compare with the normal methods, the microspheres prepared by this approach were characterized by particle size distribution and photograph of microscope. The relationship between the particle size and the instrument parameters of novel method was set up for the first time. The central composite design (CCD) was applied to study the main effects and interactions of three instrument factors on preparation of microspheres. The particle size of microspheres was below 200 mum and the shape of microspheres was spherical in nature evidenced by microscope photographs. Vinpocetine was used as the model drug to prepare the vinpocetine PLGA microspheres (VIN-PLGA-MS), and then drug loading, entrapment efficiency, scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC) and in vitro drug release behavior were examined. The results indicated that the drug loading and entrapment efficiency were increased using the novel method. The drug released slowly more than 30 days. The release behavior was fit for four kinds of kinetic model. The result indicated that release behavior was fitted by Zero-order kinetic model before release 72 hours, and was fitted with First-order kinetic model after release 72 hours. The novel method developed in our paper can give a promising way for industrialization, and the foreground was also proved by the scale-up batch experiment.

Preparation of budesonide-poly (ethylene oxide) solid dispersions using supercritical fluid technology.

The purpose of this study was to investigate the possibility of preparing solid dispersions of the poorly soluble budesonide by supercritical fluid (SCF) technique, using poly (ethylene oxide) (PEO) as a hydrophilic carrier. The budesonide-PEO solid dispersions were prepared, using supercritical carbon dioxide (SC CO(2)) as the processing medium, and characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility test and dissolution test in order to understand the influence of the SCF process on the physical status of the drug. The endothermic peak of budesonide in the SCF-treated mixtures was significantly reduced, indicating that budesonide was in amorphous form inside the carrier system. This was further confirmed by SEM and PXRD studies. The enhanced dissolution rates of budesonide were observed from SCF-treated budesonide-PEO mixtures. The amorphous characteristic of the budesonide, the better mixing of drug and PEO powders in the presence of SC CO(2), together with the improved wettability of the drug in PEO, produced a remarkable enhancement of the in vitro drug dissolution rate. Thus, budesonide-PEO solid dispersions with enhanced dissolution rate can be prepared using organic solvent-free SCF process.

Studies on bi-layer osmotic pump tablets of water-insoluble allopurinol with large dose: in vitro and in vivo.

Controlled release bi-layer osmotic pump tablets (BOPT) of water-insoluble allopurinol with large dose (150 mg/BOPT) were successfully prepared merely with sodium chloride as osmotic promoting agent and polyethylene oxide (PEO) as suspending agent. Formulations of the two kinds of agents were investigated in order to discuss their effects on the release behavior of BOPT, and then the optimal formulation was evaluated. The pharmacokinetics studies of allopurinol and its active metabolite oxypurinol in two-preparation and two-period crossover design relative to the equivalent dose of commercially common allopurinol tablets were evaluated in six Beagle dogs. And the pharmacokinetics results showed that allopurinol BOPT were able to provide a slow release of allopurinol, and oxypurinol were bioequivalent between allopurinol BOPT and common allopurinol tablets. A good in vitro-in vivo correlation of allopurinol was also proved. In conclusion, water-insoluble drugs with large dose can be designed to BOPT for efficacy and safety use.

Chitosan-based controlled porosity osmotic pump for colon-specific delivery system: screening of formulation variables and in vitro investigation.

A microbially triggered colon-targeted osmotic pump (MTCT-OP) has been studied. The gelable property at acid condition and colon-specific biodegradation of chitosan were used to: (1) produce the osmotic pressure, (2) form the drug suspension and (3) form the in situ delivery pores for colon-specific drug release, respectively. The scanning electron microscopy (SEM) study and the calculation of membrane permeability were applied to elucidate the mechanism of MTCT-OP. The effects of different formulation variables, including the level of pH-regulating excipient (citric acid) and the amount of chitosan in the core, the weight gain of semipermeable membrane and enteric-coating membrane, and the level of pore former (chitosan) in the semipermeable membrane, have been studied. Results of SEM showed that the in situ delivery pores could be formed in predetermined time after coming into contact with dissolution medium, and the number of pore was dependent on the initial level of pore former in the membrane. The amount of budesonide release was directly proportional to the initial level of pore former, but inversely related to the weight of semipermeable membrane. The effects of variations in the level of citric acid and chitosan in the core formulation on drug release were studied. The different levels of enteric-coating membrane could prevent cellulose acetate membrane (containing chitosan as pore former) from forming pore or rupture before contact with simulated colonic fluid, but had no effect on the drug release. Budesonide release from the developed formulation was inversely proportional to the osmotic pressure of the release medium, confirming that osmotic pumping was the major mechanism of drug release. These results showed that MTCT-OP based on osmotic technology and microbially triggered mechanism had a high potential for colon-specific drug delivery.

Studies of the pharmacokinetics of paeoniflorin in two Jing-Zhi-Guan-Xin formulations after oral administration to beagle dogs.

Paeoniflorin is the principal bioactive component of Paeoniae Radix. The traditional chinese medicine compound recipe (TCMCR) tablets of Jing-Zhi-Guan-Xin (JZGX), which is composed of Radix Salviae Miltiorrhizae, Radix Paeoniae Rubrae, Rhizoma Chuan-xiong, Flos Carthami and Lignum Dalbergiae Odorafera, have been widely used in China and Japan. The plasma concentrations of paeoniflorin in beagle dogs after oral administration of two Jing-Zhi-Guan-Xin formulations (the dose used in the two formulations were both 200 mg paeoniflorin) were measured using a simple and rapid HPLC method. The mean terminal half-lives (t1/2) of JZGX tablet and JZGX elementary osmotic pump tablet (EOPT) formulations of paeoniflorin were 147.52 +/- 28.98 and 276.60 +/- 24.24 min, the maximum plasma concentrations (Cmax) of paeoniflorin were 210.49 +/- 23.89 and 94.36 +/- 14.01 ng/ml, times to reach maximum concentrations (tmax) were 130.00 +/- 30.98 and 280.00 +/- 48.99 min, the area under the plasma concentration-time curves (AUC0-infinity) were 43066.50 +/- 10119.51 and 42266.87 +/- 2654.90 ng min/ml, the mean residence times (MRT) were 212.87 +/- 41.82 and 399.14 +/- 34.98 min, respectively, and the relative bioavailability (Fr) of JZGX EOPT compared with JZGX tablet was 101.8 +/- 18.8%. These results, compared with the pharmacokinetic parameters of paeoniflorin after oral administration of Paeoniae Radix extract alone, indicated that the absorption of paeoniflorin after oral administration of the two JZGX formulations was significantly greater than that after oral administration of Paeoniae Radix extract alone.