betadex and tanshinone

In this paper, tanshinone-ⅡA (Tan-IIA)/β-cyclodextrin (β-CD) inclusion complexes were prepared by saturated aqueous solution method. Based on the single factor experiment, Box-Benhnken design and response surface method were utilized to optimize the preparation procedures of tanshinone-ⅡA/β-cyclodextrin inclusion complexes. The ratio of β-CD to Tan-ⅡA, experimental temperature and time were defined as independent variables, while the yield of the inclusion complexes, encapsulation efficiency and the generalized "normalized value" were set as the response value. In addition, the inclusion complexes were characterized by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The results showed that optimum preparation conditions for Tan-ⅡA/β-CD inclusion complex were as follows: Tan-ⅡA/β-CD ratio of 1:7, the temperature of 48 ℃ and the time of 3 h. Under the optimized conditions, the encapsulation efficiency of Tan-ⅡA/β-CD inclusion complex was 84.75%. The Tan-IIA and β-CD inclusion complex can significantly improve the dissolution of Tan-ⅡA.

Topics: Abietanes; beta-Cyclodextrins; Nuclear Magnetic Resonance, Biomolecular; Solubility; Spectrum Analysis

1. The study aimed to investigate the pharmacokinetics of cryptotanshinone in a hydroxylpropyl-beta-cyclodextrin-included complex in dogs and rats. 2. Animals were administrated the inclusion complex of cryptotanshinone and the concentrations of cryptotanshinone and its major metabolite tanshinone IIA were determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. 3. Cryptotanshinone in inclusion complex was absorbed slowly after an oral dose, and the C(max) and AUC(0-)(t) were dose-proportional. The bioavailability of cryptotanshinone in rats was (6.9% +/- 1.9%) at 60 mg kg(-1) and (11.1% +/- 1.8%) in dogs at 53.4 mg kg(-1). The t(1/2) of the compound in rats and dogs was 5.3-7.4 and 6.0-10.0 h, respectively. Cryptotanshinone showed a high accumulation in the intestine, lung and liver after oral administration, while the lung, liver and heart had the highest level following intravenous dose. Excretion data in rats showed that cryptotanshinone and its metabolites were mainly eliminated from faeces and bile, and the dose recovery rate was 0.02, 2.2, and 14.9% in urine, bile, and faeces, respectively. 4. The disposition of cryptotanshinone in an inclusion complex was dose-independent and the bioavailability was increased compared with that without cyclodextrin used to formulate the drug. Cryptotanshinone was distributed extensively into different organs. Excretion of cryptotanshinone and its metabolites into urine was extremely low, and they were mainly excreted into faeces and bile.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Abietanes; Administration, Oral; Animals; beta-Cyclodextrins; Cardiovascular Agents; Dogs; Drugs, Chinese Herbal; Drugs, Investigational; Female; Male; Phenanthrenes; Phenanthrolines; Rats; Salvia miltiorrhiza; Tissue Distribution

In this paper, the effect of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the aqueous solubility, dissolution rate, and intestinal permeability of the tanshinone IIA (TS IIA) was investigated. The corresponding inclusion complex of TS IIA/HP-beta-CD at the molar ratio of 1:1 was obtained by coevaporation and characterized by differential scanning calorimetry, and X-ray diffraction. The solubility of complexed TS IIA in water at 37+/-0.1 degrees C was 17 times greater than that for the uncomplexed drug. The dissolution rate of TS IIA was significantly increased by the complexation with HP-beta-CD, due to its solubilizing activity. The everted intestinal sac technique in rats was used to study the absorption behavior of TS IIA and this complexation through the intestinal tissues. The permeability rates of TS IIA across the intestinal epithelial membrane were enhanced by the formation of inclusion complex with HP-beta-CD about 5.2, 5.8 and 4.8 times of the uncomplexed TS IIA in duodenum, jejunum and ileum, respectively. It was revealed that the absorption rate-limiting step of TS IIA might be the dissolution process. The present results indicate the potential use of HP-beta-CD to improve the gastrointestinal tract absorption of TS IIA.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Abietanes; Animals; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallography, X-Ray; Drug Carriers; Drug Compounding; Drugs, Chinese Herbal; Duodenum; Ileum; In Vitro Techniques; Intestinal Absorption; Intestine, Small; Jejunum; Kinetics; Male; Permeability; Phenanthrenes; Rats; Rats, Sprague-Dawley; Solubility; Technology, Pharmaceutical; Water

In this paper, the effect of the chemically modified cyclodextrin [namely, 2-hydroxypropyl-beta-cyclodextrin, (HP-beta-CD)] on the aqueous solubility, dissolution rate, and intestinal permeability of the tanshinone IIA (TS) was investigated. The corresponding inclusion complex of TS-HP-beta-CD at the molar ratio of 1:1 was obtained by coevaporation. The solubility of complexed TS in water at 37+/-0.1 centi-degree was 17 times greater than that for the uncomplexed drug. The dissolution rate of TS was significantly increased by the complexation with HP-beta-CD, due to its solubilizing activity. The everted intestinal sac technique in rats was used to study the absorption behavior studies of TS and this complexation through the intestinal tissues. The permeability rates of TS across the intestinal epithelial membrane were enhanced by the formation of inclusion complex with HP-beta-CD about 89, 97 and 82 times of the uncomplexed TS in duodenum, jejunum and ileum, respectively. It was revealed that the absorption rate-limiting step of TS might be the dissolution process. The present results indicated the potential use of HP-beta-CD to improve the gastrointestinal tract absorption of TS.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Abietanes; Animals; beta-Cyclodextrins; Drug Stability; Drugs, Chinese Herbal; Excipients; In Vitro Techniques; Intestinal Absorption; Intestine, Small; Male; Phenanthrenes; Rats; Rats, Sprague-Dawley; Solubility

In this paper, the intestinal permeability of the inclusion complex of tanshinone IIA (TS IIA) with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was investigated. The corresponding complexation of TS IIA-HP-beta-CD was obtained by coevaporation and characterized by differential scanning calorimetry and X-ray diffraction. The recirculation intestinal perfusion technique in rats was used to study the absorption behavior of free and complexed TS IIA. The change of concentration of TS IIA was separately calculated according to Michaelis-Menten and the Fick's equation to investigate its absorption rate-limiting step. Using the mathematical models above, it was concluded that the limit step to absorption of TS IIA was the dissolution process. Different concentrations of complexed TS IIA were administrated to three intestinal segments, with the intestinal permeability ranging from 3.16x10(-5) cm.s(-1) in the duodenum (50 microg.ml(-1)) to 4.11x10(-5) cm.s(-1) in the jejunum (100 microg.ml(-1)). With the increase of dosage of complex, TS IIA's absorption did not show saturated phenomenon, suggesting its transport mechanism in vivo might primary be passive transport. Besides, the permeability of TS IIA was not apparently influenced by the perfusion section studied, which indicated that there might not exist specific absorption site for TS IIA.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Abietanes; Algorithms; Animals; beta-Cyclodextrins; Biological Availability; Calorimetry, Differential Scanning; Chromatography, High Pressure Liquid; Data Interpretation, Statistical; Indicators and Reagents; Intestinal Absorption; Male; Models, Statistical; Permeability; Phenanthrenes; Rats; Rats, Sprague-Dawley; Solutions; X-Ray Diffraction

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.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Abietanes; beta-Cyclodextrins; Biological Transport; Chromatography, High Pressure Liquid; Intestinal Absorption; Phenanthrenes; Salvia miltiorrhiza

Solid inclusion complexes of two tanshinones (Tans): tanshinone IIA (Tan IIA), tanshinone I (Tan I) with beta-cyclodextrin (beta-CD) were synthesized by coprecipitation method. The solid inclusion complexes were characterized by using several analytical techniques: (1)H NMR spectra, IR spectra and thermal analysis. Stoichiometry of the inclusion complexes of Tans with beta-CD or HP-beta-CD is 1:1 which was investigated in solution. The formation constants of the complexes were determined by UV spectrophotometry. For same kind of CD, the stability was in the order: Tan IIA > Tan I; for same guest, the stability was in the order: HP-beta-CD > beta-CD. The effect of temperature on the inclusion interaction was examined and the thermodynamic parameters of inclusion process, Delta G, Delta H, Delta S were determined as well. The experimental results indicate that the inclusion process was an exothermic and enthalpy-driven process accompanied with a negative entropic contribution. The inclusion interaction between CD and Tans satisfied the law of enthalpy-entropy compensation.

Topics: Abietanes; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemical Precipitation; Magnetic Resonance Spectroscopy; Molecular Structure; Phenanthrenes; Spectroscopy, Fourier Transform Infrared; Temperature; Thermodynamics

With the preparation of borneol-beta-cyclodextrin inclusion compound, the stability of the product was improved. In the studies on quality standards, TLC method was used in the identification of three medicinal ingredients and TLC-ultraviolet spectrophotometry was used in the content determination of the chemical constituent tanshinone II A in Salvia miltiorrhiza.

Topics: Abietanes; beta-Cyclodextrins; Chromatography, Thin Layer; Cyclodextrins; Drug Combinations; Drugs, Chinese Herbal; Excipients; Phenanthrenes; Phenanthrolines; Plant Extracts; Quality Control; Salvia miltiorrhiza; Spectrophotometry, Ultraviolet; Technology, Pharmaceutical