OBJECTIVE:To determine the retative bioavailability of Diclofenac sodium eye-ointment in rabbit eyes and to evaluate its pharmacokinetics following topical application METHODS:48 rabbits were divided into two groups 0 1% Diclofenac sodium eye-ointment and Diclofenac sodium eyedrops were applied topically to rabbit eyes and aqueous humor and iridic tissue were collected at given times The concentration of Diclofenac sodium in tissue were measured by HPLC RESULTS:Diclofenac sodium eye-ointment group had higher concentration and longer half-time than Diclofenac sodium eyedrops group,however,the peak time were the same in two groups The relative bioavailabilities of Diclofenac sodium ointment in aqueous humor and iridic tissue were 183 33% and 205 68% respectively,compared with those of Diclofenac sodium eyedrops CONCLUSION:Diclofenac sodium eye-ointment can be absorbed well and released slowly,which can reduce the frequency of application of drug It is especially suitable for operation patient or application at night

Objective To prepare the solid dispersion of ginsenoside Rg3 with different carriers and measure their solubility and dissolution characterisitics. Methods The solid dispersion of ginsenoside Rg3 was prepared by the melted and dissolved methods with Poloxamer 188(F68), PVP k29/32, and PEG 6000 as carriers, respectively. The equilibrium solubility and dissolution characteristics of the solid dispersion in vitro were measured by HPLC. The existing state of ginsenoside Rg3 in the solid dispersion was identified by the differential scanning calorimetery. Results The ginsenoside Rg3 was completely dispersed in carrier and formed a mixture with carriers. The solubility and dissolution rates of all solid dispersion were increased obviously. Conclusion The solid dispersion of ginsenoside Rg3 with Poloxamer 188 as carriers is better on improving dissolution and solubility than those with PVP and PEG 6000 as carriers.

OBJECTIVE:To determine the valsartan concentration in human plasma METHODS:The plasma sample was extracted with a liquid-solid method and determined with HPLC,stationary phase was Hypensil ODS C18(4 6nm?200nm,5?m),mobile phase consisted of acetonitrile and 0 01mol/L KH2PO4 buffer(pH 2 8)(50∶50) The flow rate was 1 5ml/min Detection was performed with fluorescence detector at ?ex 265nm,?em 378nm RESULTS:The retention time of valsartan was about 5 4 minutes,and the linear range of quantity was 0 05～5?g/ml The recoveries of methodology were more than 90%(n=5) Inter-day and intra-day RSD were less then 10%(n=5) CONCLUSION:This method is rapid and accurate It can be applied to determining the plasma valsartan concentration and studying on pharmacokinetics

OBJECTIVE:To establish the method for simultaneous contents determination of 5 kinds of acid and alkaline componentsin anti-cold compound preparation. METHODS:HPLC method was adopted. The workstation was Auto·Blend Plus software of ACQUITY Arc system. The determination was performed on Discovery?HS F5-5 column with mobile phase consisted of acid mixture-base mixture-methanol-0.3% triethylamine (gradient elution) at the flow rate of 1.0 mL/min. The detection wavelengths were set at 270 nm (acetaminophen,salicylamide,chlorphenamine maleate,triprolidine hydrochloride) and 299 nm (aspirin). The column temperature was 35 ℃,the sample size was 20 μ L. RESULTS:The linear ranges of acetaminophen, salicylamide,acetylsalicylic acid,chlorphenamine maleate,triprolidine hydrochloride were 26-411 μ g/mL(r＝0.999 6),16-254 μg/mL(r＝0.999 8),16-748 μg/mL(r＝0.998 1),35-565 μg/mL(r＝0.999 8)and 25-404 μg/mL(r＝0.999 7),respectively. LOQ were 3.6,3.1,4.0,9.6,6.3 μ g/mL;LOD were 1.9,1.3,1.4,2.9,2.3 μ g/mL,respectively. RSDs of intermediate precision, stability and reproducibility tests were all lower than 2%. Average recoveries were 100.0%-102.0%(RSD＝0.59%,n＝9), 95.2%-101.0%(RSD＝1.55%,n＝9),96.2%-99.9%(RSD＝1.24%,n＝9),96.2%-101.5%(RSD＝1.57%,n＝9),96.3%-98.9%(RSD＝0.83%,n＝9),respectively. RSDs of durability tests were lower than 3%. CONCLUSIONS:The method is simple, accurate,precise,stable,reproducible and durable,and can be used for simultaneous contents determination of 5 kinds of acid and alkaline components in anti-cold compound preparation.

OBJECTIVETo establish the model of microdialysis, and study the ocular pharmacokinetics of puerarin in anesthetic rabbits.

METHODImplanted the probe into anterior chamber of anesthetic rabbit by surgery. After balanced for 2 h, 1% puerarin eye drop (100 microL) was applied into the cul-de-sac with micropipette. Immediately the dialysate was collected at different time and detected by HPLC with the detection wavelength of 249 nm. The mobile phase was methanol and 0.1% citric acid solution (30:70); the flow rate was 1.0 mL x min(-1).

RESULTAfter the administration, puerarin can be absorbed into aqueous humor quickly. The peak concentration of puerarin appeared at about 1 h and then reduced gradually. The peak concentration(C(max)) is (2.52 +/- 0.31) mg x L(-1). The other lower peak was shown at 3.5 h during the eliminate phase. This might be attributed to the inhibition of aqueous humor production by the puerarin and resulted in a high drug concentration. The area under concentration-time curve (AUC(0-t)) is (5.04 +/- 0.21) mg x h x L(-1) and the eliminate half life (t1/2) is (0.38 +/- 0.13) h.

CONCLUSIONThe microdialysis technique can be used to detect the ocular pharmacokinetics of puerarin, and support the valuable pharmacokinetics parameter for the clinical applications of puerarin eye drop.

Anesthesia ; Animals ; Eye ; metabolism ; Female ; Isoflavones ; pharmacokinetics ; Male ; Microdialysis ; methods ; Ophthalmic Solutions ; Rabbits

OBJECTIVETo study the corneal penetration of PAMAM dendrimers-coated puerarin liposomes in rabbits.

METHODEvaluated PAMAM (G2, G3) dendrimers-coated puerarin liposomes were prepared and the in vitro transcorneal penetration were compared to puerarin drop solution and uncoated liposomes. The effect of different proportion of PAMAM to phospholipids in formulation on corneal penetration and the penetration parameters were investigated.

RESULTThe steady state fluxes and permeability coefficients of puerarin by PAMAM G2 (1.0%) and PAMAM G3 (0.5%) coated puerarin liposomes were greater than that by puerarin drop solution and uncoated liposomess (P < 0.01), meanwhile the PAMAM G2 (1.0%) and PAMAM G3 (0.5%) coated liposomes were better than other ratios of coated liposomes for improvement of corneal penetration (P < 0.01).

CONCLUSIONThe PAMAM coated liposomes is able to enhance the corneal penetration of puerarin and promising as an ocular drug carriers.

Animals ; Cornea ; metabolism ; Dendrimers ; chemistry ; metabolism ; In Vitro Techniques ; Isoflavones ; chemistry ; Liposomes ; chemistry ; metabolism ; Rabbits

OBJECTIVE:To prepare Bevacizumab(BEV)multivesicular liposomes(BEV-MVLs)with sustained-effect,and to study their in vitro release characteristics. METHODS:BEV-MVLs were prepared by double emulsion method. Box-Behnken design-response surface methodology was used to optimize the prescription with the concentration of glycerol trioleate(TO)in organic phase,ratio of 1,2-dioleoyl-sn-glycero-3-phosphocholine(DOPC)-cholesterol(CH)(mol/mol),the concentration of L-lysine in external water phase as factors,using encapsulation rate as index. The morphology of BEV-MVLs was observed by inverted fluorescence microscope and SEM;particle size was determined by laser particle size analyzer;the BEV content was determined by HPLC and calculate the encapsulation rate and in vitro accumulative release rate.RESULTS:The optimized prescription was as follows as TO of 2.72 mmol/L in organic phase,DOPC-CH ratio of 0.67(mol/mol)and L-lysine of 40 mmol/L in external water phase. The encapsulation rate of BEV-MVLs was(80.65±4.42)%(n=3),and relative error of it to predicted value was 2.54%. The liposomes were spherical in appearance shape and uniform in size,and they were typical non-concentric vesicle structure with average particle size of 16.80 μm. 30 d in vitro accumulative release rate was about 92%. CONCLUSIONS:Prepared BEV-MVLs show sustained-effect,and their encapsulation rate reaches the expected effect.

Folic acid(FA)was conjugated with bovine serum albumin(BSA)to form targeting material. BSA-coated cationic nanostructure lipid carriers(BSA-cNLCs)and folate-BSA-coated cationic nanostructure lipid carriers(FA-BSA-cNLCs)were prepared by film dispersion. The particle sizes of BSA-cNLCs and FA-BSA-cNLCs were 81. 4 nm and 79. 8 nm, while their Zeta potentials were +5. 12 mV and +3. 74 mV. Both nanostructure lipid carriers showed spherical shape. Paclitaxel encapsulation efficiency of them were more than 97%, with drug loading efficiency of about 3. 7%. In vitro experiments confirmed that the uptake of FA-BSA-cNLCs by overexpressed folate receptor SKOV3 cells was significantly higher than that of BSA-cNLCs, demonstrating that FA-BSA-cNLCs were obviously targeted to SKOV3. Blood and tumor pharmacokinetics showed that there was no significant differences between BSA-cNLCs and FA-BSA-cNLCs. This suggested that modified FA on the surface of the preparation had no effect on its in vivo behavior. Tumor inhibition of BSA-cNLCs and FA-BSA-cNLCs were 72. 08% and 80. 75%, repectively, which indicateds that FA-BSA-cNLCs improve anticancer efficacy in vitro and in vivo, and that it could be a potential preparation for the treatment of cancer.

Hypoxia is a serious impediment to current treatments of many malignant tumors. Catalase, an antioxidant enzyme, is capable of decomposing endogenous hydrogen peroxide (H

BACKGROUND: Afatinib, a second-generation irreversible epidermal growth factor inhibitor receptor for the development of non-small cell lung cancer and secondary drug resistance, has low bioavailability and adverse reactions due to current oral administration. The aim of this study was to prepare a novel drug delivery system, afatinib liposome, and to establish a method for the determination of encapsulation efficiency. METHODS: Four different preparation methods were used to prepare afatinib liposomes, and the optimal preparation process was determined by comparing the encapsulation efficiency and particle size. RESULTS: It has been verified that sephadex microcolumn centrifugation can be used to purify afatinib liposomes, and UV spectrophotometry can be employed to determine the entrapment efficiency of liposomes. Among different preparation methods, the encapsulation efficiency of afatinib liposomes prepared by ammonium sulfate gradient method was 90.73% and the average particle size was 108.6 nm. CONCLUSIONS Ammonium sulfate gradient method can be successfully applied to prepare afatinib liposomes that performed higher encapsulation efficiency and smaller particle size. The UV spectrophotometry employed to determine the liposome encapsulation efficiency was easy operation and with high accuracy.
Afatinib ; Capsules ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Drug Compounding ; methods ; Liposomes ; Lung Neoplasms ; drug therapy ; Quinazolines ; administration & dosage ; chemistry ; therapeutic use