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

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

AIMTo investigate the complexation of prostaglandin E1 (PGE1) with hydroxylpropyl-beta-cyclodextrin (HP-beta-CD) in aqueous solutions, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters during the complexation process.

METHODSThe measurements of the complexation mechanism, inclusion molar ratio of the host and guest molecules and change of thermodynamic parameters were carried out by the following methods separately: phase solubility method, UV absorption spectroscopy, circular dichroism spectroscopy, equimolar series method and thermodynamic method, respectively.

RESULTSThat all the phase solubility diagrams showed a typical AL-type in various pH buffered solutions, suggested the formation of a soluble complex of 1:1 molar ratio. Both UV absorption spectroscopy and circular dichroism spectroscopy confirmed that the significant interaction between the host and guest molecules was probably due to the inclusion of chromophore moiety of PGE1 molecule into the hydrophobic cavity of HP-beta-CD molecule. The change in the thermodynamic parameters suggested that the complexation could proceed spontaneously along with the release of heat and the decrease of entropy.

CONCLUSIONAn 1:1 molar ratio inclusion complex of PGE1 with HP-beta-CD could be formed spontaneously and, hence, the solubility of PGE1 in aqueous solution increased. Appropriate temperature and suitable media pH probably favor the progress of complexation procedure.

2-Hydroxypropyl-beta-cyclodextrin ; Alprostadil ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration ; Solubility ; Technology, Pharmaceutical ; methods ; Temperature ; beta-Cyclodextrins ; administration & dosage ; chemistry

Rutaecarpine (Rut) is a type of indole quinazoline alkaloid exracted from Ruticarpum. Studies showed that Rut has a wide range of pharmacological effects, such as anti-hypertension, anticancer, anti-inflammation, anti-thrombus formation. Currently, many scholars are committed to developing it into a new antihypertensive and anti-inflammatory drug with all new mechanisms. But studies found that Rut is a highly fat-soluble drug with low water and oil solubility. Its high insolubility is the main obstacle in its oral absorption and application, which greatly reduced its bioavailability. Therefore, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was used as the inclusion material to prepare Rut-HP-beta-CD inclusion complex in this experiment, in order to increase its water solubility and bioavailability. In this experiment, the inclusion complex was prepared by the stirring-freeze-dry method. The preparation process was optimized by the orthogonal test, with the inclusion rate as the index, and molar ratio between host and guest molecules, inclusion temperature, time and stirring speed as the impacting factors. Moreover, the inclusion complex was verified by detecting the apparent solubility, thin layer chromatography, microscopic identification, melting point detection and dissolution study. The results showed that under the conditions of the molar ratio between Rut and HP-beta-CD of 1: 1, temperature at 60 degrees C, inclusion time of 4h and stirring speed at 600 r x min(-1), the inclusion rate of Rut-HP-beta-CD reached 91.04%. Therefore, the preparation process of Rut-HP-beta-CD inclusion under the optimum conditions is simple and feasible, with a highest inclusion rate and reproducibility, and could significantly improve Rut's solubility and bioavailability, and provide a reliable experimental basis for its clinical application.
2-Hydroxypropyl-beta-cyclodextrin ; Alkaloids ; chemistry ; Chemistry, Pharmaceutical ; methods ; Drug Carriers ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Rutaceae ; chemistry ; Solubility ; beta-Cyclodextrins ; chemistry

AIMTo perpare and identify irisquinone hydroxypropyl-beta-cyclodextrin inclusion complex (irisquinone-HP-beta-CD), as well as to study the inclusion mechanism and molecule stoichiometry between irisquinone and hydroxypropyl-beta-cyclodextrin.

METHODSIrisquinone-HP-beta-CD was prepared by freeze-drying technique. The ratio of host and guest was also studied in inclusion process by mol gradient and continuing variational methods. At the same time, the inclusion complex was identified by X-ray diffraction (XRD) and differential scanning calorimetry (DSC).

RESULTSIt was demonstrated that the solubility of irisquinone was enhanced markedly by inclusion with HP-beta-CD when stoichiometry was 2:1 of host and guest at 25 degrees C, 35 degrees C and 45 degrees C.

CONCLUSIONThe solubility and stability of irisquinone could be increased by preparing the inclusion complex with hydroxypropyl-beta-cyclodextrin.

2-Hydroxypropyl-beta-cyclodextrin ; Benzoquinones ; administration & dosage ; chemistry ; Calorimetry, Differential Scanning ; Drug Compounding ; methods ; Drug Stability ; Freeze Drying ; Solubility ; X-Ray Diffraction ; beta-Cyclodextrins ; administration & dosage ; chemistry

OBJECTIVETo synthesize a (2-Hydroxypropyl)-γ-cyclodextrin-polyethylenimine/adamantane-conjugated doxorubicin (γ-hy-PC/Ada-Dox) based supramolecular nanoparticle with host-guest interaction and to identify its physicochemical characterizations and antitumor effect.

METHODSA novel non-viral gene delivery vector γ-hy-PC/Ada-Dox was synthesized based on host-guest interaction. 1H-NMR, NOESY, UV-Vis, XRD and TGA were used to confirm the structure of the vector. The DNA condensing ability of complexes was investigated by particle size, zeta potential and gel retardation assay. Cytotoxicity of complexes was determined by MTT assay in BEL-7402 and SMMC-7721 cells. Cell wound healing assay was performed in HEK293 and BEL-7404 cells. The transfection efficiency was investigated in HEK293 cells. H/E staining and cell uptake assay was performed in BEL-7402 cells.

RESULTSThe structure of γ-hy-PC/Ada-Dox was characterized by 1H-NMR, NOESY, UV-Vis, XRD, TGA. The drug loading was 0.5% and 5.5%. Gel retardation assay showed that γ-hy-PC was able to completely condense DNA at N/P ratio of 2; 0.5% and 5.5% γ-hy-PC/Ada-Dox was able to completely condense DNA at N/P ratio of 3 and 4,respectively. The cytotoxicity of polymers was lower than that of PEI25KDa. The transfection efficiency of γ-hy-PC was higher than that of γ-hy-PC/Ada-Dox at N/P ratio of 30 in HEK293 cells; and the transfection efficiency was decreasing when Ada-Dox loading was increasing. Cell uptake assay showed that γ-hy-PC/Ada-Dox was able to carry drug and FAM-siRNA into cells.

CONCLUSIONThe novel vector γ-hy-PC/Ada-Dox has been developed successfully, which has certain transfection efficiency and antitumor activity.

2-Hydroxypropyl-beta-cyclodextrin ; Adamantane ; administration & dosage ; pharmacology ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Doxorubicin ; administration & dosage ; pharmacology ; Genetic Vectors ; Humans ; Nanoparticles ; Polyethyleneimine ; Transfection ; beta-Cyclodextrins

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