OBJECTIVETo determine the major factors affecting the conversion efficiency of naringin-HP-beta-CD that was enzymed to prepare naringenin were determined and select the process condition with high conversion efficiency, stable and suitable for industrial production.

METHODThe dropping method was used to prepare naringin-HP-beta-CD, which was hydrolyzed by snailase to obtain naringenin. With the bioconversion rate as the index, the effects of pH value, temperature, reaction time, dosage of enzyme and concentration of naringin-HP-beta-CD on conversion rate of naringenin were detected for the purpose of optimizing the preparation condition. the conversion efficiency of naringin-HP-beta-CD was verified by scanning calorimetry, and the Hydrolysis product was identified by H-NMR, and 13C-NMR.

RESULTThe optimum enzymolysis of naringin-HP-beta-CD with snailase was 98.4% under the conditions of 37 degrees C, a pH 5.0 acetic acid- sodium acetate buffer solution for 12 hours. The substrate concentration was 30 g x L(-1) and the weight ratio of enzyme and substrate was 3: 5. Under the optimum enzymolysis condition, the conversion rate of naringin-HP-beta-CD was higher than naringin that was not entrapped with HP-beta-CD, with 272.25 reaction product relative molecules. The structure of naringenin was confirmed by the analysis of 1H-NMR and 13C-NMR.

CONCLUSIONNaringin which is entrapped with HP-beta-CD to prepare naringenin can significantly improve the conversion efficiency by shortening the reaction time, increasing the concentration of the substrate and reducing the amount of enzyme. Therefore, the process is stable and it was suitable for industrialization.

2-Hydroxypropyl-beta-cyclodextrin ; Flavanones ; chemistry ; isolation & purification ; Hydrolysis ; Solubility ; beta-Cyclodextrins ; chemistry

AIMTo investigate the combined effect of cosolvent and cyclodextrin (CD) on solubilization of insoluble drugs.

METHODSPhase-solubility method was applied to determine solubilization of two diterpenoids in cosolvent / cyclodextrin combinations. The combined effect was evaluated and explained with an established mathematical model, and the model parameters were calculated by means of nonlinear regression analysis.

RESULTSThe strong agreement between the predicted and the observed solubility data supports the validity of the proposed model, with the determination coefficients of two regression models were 0.993 and 0.992, separately.

CONCLUSIONThe validated mathematical model can be used to explain and predict the combined solubilization of the two insoluble drugs in different cosolvent systems.

2-Hydroxypropyl-beta-cyclodextrin ; Algorithms ; Diterpenes ; chemistry ; Models, Chemical ; Solubility ; Solvents ; chemistry ; Water ; chemistry ; beta-Cyclodextrins ; chemistry

Taking Tanshinon IIA as the target and using reversed phase high performance liquid chromatography,we have developed a rapid and sensitive assay for lipophilic components of Danshen (LCD) in perfusate. The model of intestinal absorption was used to determine the concentration of Tanshinon IIA in rats as an in situ model. The change of concentration of Tanshinon IIA was separately calculated according to Michaelis-Menten and the Fick's equation to investigate the absorptive limit step of the LCD. It was concluded that the limit step to absorption of LCD was at the dissolution, by assessing the fitting index or correlative index. On the basis of the conclusion, the experiment was designed to prepare the inclusive complex of the LCD with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and to study its absorptive mechanism. With the increase of dosage of complex, its absorption did not show saturated phenomenon in gastro-intestinal tract in rats and the constant Ka did not show significant difference, suggesting that the transport of mechanism in vivo is similar to passive transport.
2-Hydroxypropyl-beta-cyclodextrin ; Biological Transport ; Chromatography, High Pressure Liquid ; Diterpenes, Abietane ; Intestinal Absorption ; Phenanthrenes ; isolation & purification ; pharmacokinetics ; Salvia miltiorrhiza ; chemistry ; beta-Cyclodextrins ; chemistry ; pharmacokinetics

OBJECTIVETo prepare a novel floating micropellets containing hydroxy propyl-beta-oyclodextrin(puerarin-HP-beta-CD) for gastroretentive dosage form and evaluate its pharmaceutical characteristics in vitro.

METHODThe puerarin HP-beta-cyclodextrin inclusion complex was prepared by freeze-drying method. Puerarin and its HP-beta-CD inclusion complex were incorporated into alginate beads, respectively. The effect of methyl cellulose (MC), Mg-Stearate and chitosan on buoyancy and cumulative release rate of puerarin were investigated in simulated gastric fluid.

RESULTThe spectrums of FTIR and profiles of X-ray powder diffraction of samples proved the formation of inclusion complex between puerarin and HP-beta-CD. Magnesium stearate had a significant effect on the buoyancy of micropellets, and satisfied results were gained by the content with 2%. The solubility of puerarin was increased 65.6-fold by the formation of inclusion complex, the dissolution rate and cumulative release percentage also improved significantly although with the burst release phenomena. The micropellets showed sustained release properties by using puerarin-HP-beta-CD inclusion complex mixed with puerarin (1:1) and treated thoroughly under homogenizer.

CONCLUSIONThe solubility and release rate of puerarin are increased by the formation of inclusion complex with HP-beta-CD and its gastroretentive dosage forms displayed satisfied floating and sustained release characteristics.

2-Hydroxypropyl-beta-cyclodextrin ; Dosage Forms ; Freeze Drying ; Isoflavones ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction ; beta-Cyclodextrins ; chemistry

OBJECTIVETo prepare an inclusion complex of daidzein and hydropropyl-beta-cyclodextrin to enhance the solubility of daidzein.

METHODThe inclusion complex of daidzein was prepared by the solution stirring method. The binary system of daidzein and HP-beta-CD was confirmed by differential thermal, thermogravimetry analysis, infrared spectroscopy and X-ray diffractometry.

RESULTThe drug content in the inclusion complex was 6. 76% and the solubility was 13.68 mg x mL(-1). The identification results showed that the inclusion complex was formed.

CONCLUSIONThe preparation method of the inclusion complex of daidzein and hydropropyl-beta-cyclodextrin is simple and available, with a increased solubility of daidzein.

2-Hydroxypropyl-beta-cyclodextrin ; Differential Thermal Analysis ; Drug Compounding ; methods ; Isoflavones ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction ; beta-Cyclodextrins ; chemistry

OBJECTIVETo compare the pharmacokinetic parameters of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex and free evodiamine suspension in rats, and investigate the pharmacokinetic characteristics of evodiamine inclusion complex.

METHODSBoth water solubility and cumulative release percentage of EHD were tested with evodiamine as the control. Blood samples were collected from the venous plexus of SD rats after intravenous administration with evodiamine inclusion complex and free evodiamine at 100 mg/kg (equivalent evodiamine dose). Plasma concentrations of evodiamine were determined by high-performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated using DAS 2.1.1.

RESULTSThe evodiamine inclusion complex showed a better water solubility (18.46±0.36 µg/mL) and a higher cumulative release percentage [(76.8±4.9)%] than free evodiamine. The pharmacokinetic parameters of evodiamine inclusion complex and free evodiamine in rats were as follows: Cmax, 252.5±12.43 vs 161.3±3.45 µg/L; T(max), 4.00±0 vs 4.07±0 h; MRT(0-∞), 8.46±0.91 vs 4.43±0.74 h; AUC(0-t), 2266.40±28.64 vs 911.92±8.53 µg·L(-1)·h(-1); AUC(0-∞), 2359.76±31.58 vs 919.16±9.73 µg·L(-1)·h(-1). The relative bioavailability of evodiamine inclusion complex was 256.73%.

CONCLUSIONCompared with free evodiamine, evodiamine inclusion complex has a higher bioavailability.

2-Hydroxypropyl-beta-cyclodextrin ; Animals ; Biological Availability ; Chromatography, High Pressure Liquid ; Quinazolines ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Solubility ; beta-Cyclodextrins ; pharmacokinetics

OBJECTIVETo prepare cryptotanshinone (CT)-cyclodextrin inclusion compound and improve dissolution of CT.

METHODInclusion ratio was determined by plotting the phase solubility curve of CT versus hydroxypropyl-beta-cyclodextrin (HPCD). CT-cyclodextrin inclusion compound was made by wet grinding method. Properties of the inclusion compound was investigated by in vitro dissolution test, DTA and IR spectrum.

RESULTInclusion ratio of CT versus HPCD was 1:1. Dissolution of CT-HPCD inclusion compound at 45 min was 21.6 times of material drug.

CONCLUSIONDissolution of CT was improved remarkably in CT-HPCD inclusion compound. The complexation force of the inclusion compound was hydrogen bond formed by carbonyl group of CT and hydroxyl group of HPCD.

2-Hydroxypropyl-beta-cyclodextrin ; Biological Availability ; Drug Carriers ; Drugs, Chinese Herbal ; chemistry ; Phenanthrenes ; chemistry ; isolation & purification ; Salvia miltiorrhiza ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods ; Time Factors ; beta-Cyclodextrins ; chemistry

OBJECTIVETo study the solubilization effect of 2-hydroxypropyl-beta-cyclodextrin(HPCD) on paeonolum at various pH value.

METHODPhase-solubility method was adopted to study the solubilization effect at 25 degrees C and UV spectrohotometer was used to determine paeonolum content.

RESULTSThe apparent solubility of paeonolum was significantly enhanced by increased HPCD concentration. The apparent stability constant of paeonolum compounds was calculated up to 1 425 in which pH was 3 and HPCD concentration was 133.33 mmol x L(-1). The solubility of paeonolum came up to 10 mg x mL(-1).

CONCLUSIONHPCD is an ideal solubilizer for paeonolum.

2-Hydroxypropyl-beta-cyclodextrin ; Acetophenones ; administration & dosage ; chemistry ; isolation & purification ; Drug Stability ; Excipients ; Hydrogen-Ion Concentration ; Paeonia ; chemistry ; Plants, Medicinal ; chemistry ; Solubility ; beta-Cyclodextrins

OBJECTIVETo study the cyclodextrin inclusion complexes of Dragon's blood for improving the drug solubility and the preparation.

METHODThe inclusion complexes were prepared with beta-cyclodextrin, HP-beta-cyclodextrin, SBE-beta-cyclodextrin and confirmed by DTA. The activity of the inclusion complex was tested by animal experiments. Inclusion complexes tablets were prepared and the dissolution test was performed.

RESULTThe solubility of inclusion complexes was increased to 13. 75-168. 39 times. The activity of the inclusion complex was markedly improved, and dissolution rate was 78.69%.

CONCLUSIONThe cyclodextrin inclusion complexes of Dragon's blood have a good solubility, dissolution rate and pharmacological activity.

2-Hydroxypropyl-beta-cyclodextrin ; Cyclodextrins ; chemistry ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; Plant Extracts ; chemistry ; Solubility ; Tablets ; chemistry ; beta-Cyclodextrins ; chemistry

OBJECTIVETo prepare coated tablets of glycyrrhetinic acid and hydroxypropyl-beta-cyclodextrin (GTA-HP-beta-CYD) inclusion complex tablets for colon-specific release.

METHODIn order to improve the solubility of GTA, the GTA-HP-beta-CYD inclusion complex was prepared by ultrasonic-lyophilization technique and its formation were characterized by X-ray powder diffraction profiles and infrared spectrometry. The effects of inclusion condition on the inclusion efficiency and stability coefficient of inclusion complex were investigated, respectively. After prepared GTA-HP-beta-CYD tablets by powder direct compression, the pH dependant polymer Eudragit III and/or mixed with Eudragit II were used for further coating materials in fluid-bed coater. The influences of coating weight on the GTA release in different pH conditions were evaluated to establish the method for prepering colon specific delivery tablets with pulsed release properties.

RESULTThe formation of inclusion complexes were proved by X-ray powder diffraction profile and phase solubility curve. The effect of pH value of solvent was played critical role on the preparation of GTA- HP-beta-CYD inclusion complex. And the inclusion efficiency of GTA was 9. 3% and the solubility was increased to 54. 6 times at optimized method. The Eudragit III coated GTA- HP-beta-CYD tablets with coating weight 10% and 16% were showed pH dependant colon specific release profiles with slow release rate. The release profile of tablets coated with the mixture of Eudragit II and Eudragit III (1:2) were indicated typical pH dependant colon specific and pulsed release properties while the coating weight was 17%.

CONCLUSIONThe preliminary method for preparation of colon specific release tablets containing glycyrrhetinic acid with improved solubility was established for further in vivo therapeutic experiment.

2-Hydroxypropyl-beta-cyclodextrin ; Animals ; Colon ; chemistry ; Drug Stability ; Glycyrrhetinic Acid ; chemistry ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Spectrophotometry, Infrared ; Tablets ; chemistry ; X-Ray Diffraction ; beta-Cyclodextrins ; chemistry ; pharmacokinetics