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

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

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 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

AIMTo establish a simple, rapid and accurate electroanalytical method for water soluble porphyrin meso-tetrakis-(4-sulfonatophenyl) porphyrin (TPPS4); to clarify the reaction between water soluble porphyrins and bovine serum albumin (BSA); and to determine the interaction of TPPS4 with BSA in the absence of presence of cyclodextrins (CDs), separately.

METHODSThree methods including LSV, UV spectroscopy and fluorescence spectroscopy had been employed to the relevant experiments. The way of employing three methods at the same time could make the experiment results more reliable.

RESULTSIn the supporting electrolyte of NaH2 PO4-Na2 HPO4 (pH 7.18), a sensitive reduction peak of TPPS4 was found by linear sweep voltammetry (LSV), the peak potential (Ep) was -0.70 V (vs SCE). The relationship between the second derivative peak of LSV (ip") and the concentration of TPPS4 was linear from 1.0 x 10(-7) mol x L(-1) to 1.0 x 10(-5) mol x L(-1), the square of correlation coefficients (r2) were 0.998 3 and 0.999 3, respectively. The relative standard deviation (RSD) was 0.56% (n = 5). The mean recovery of TPPS4 was 99.59%. In NH4Cl-NH3 x H2O buffers (pH 9.05), it was proved that BSA and TPPS4 could interact with each other and form 1 : 1 TPPS4-BSA supramolecular system. Moreover, the interaction between TPPS4 and BSA had been investigated by adding cyclodextrins (CDs). The interaction of TPPS4 with BSA was facilitated both by hydroxypropyl-beta-CD (HP-beta-CD) and sulforbutylether-beta-CD (SBE-beta-CD).

CONCLUSIONAn electroanalytical method for TPPS4 has been established by LSV. The porphyrin drugs included by CDs could react with protein existing inside the human body easier. The consequences of this article also show that CDs will play important role in controlling and releasing the porphyrin drugs.

2-Hydroxypropyl-beta-cyclodextrin ; Electrochemistry ; methods ; Electrodes ; Porphyrins ; chemistry ; metabolism ; Protein Binding ; Serum Albumin ; chemistry ; metabolism ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; beta-Cyclodextrins ; chemistry ; metabolism

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 penetrating rate of muscone in different inclusion complexes and liposome.

METHODThe transdermal effect of muscone in different inclusion complexes and liposome was studied comparatively on mouse [corrected] skin with 40% EtOH as the absorption solution and with an improved Franz diffuse cell.

RESULTAmong the different inclusion complexes and liposome, the penetrating rate of muscone in the HP-beta-cyclodextrin inclusion and the liposome were higher than muscone, and that of muscone in the beta-cyclodextrin inclusion is the lowest.

CONCLUSIONThe HP-beta-cyclodextrin inclusion and the liposome can hence the muscone transdermal speed.

2-Hydroxypropyl-beta-cyclodextrin ; Animals ; Cycloparaffins ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Stability ; In Vitro Techniques ; Liposomes ; Mice ; Skin Absorption ; beta-Cyclodextrins