Complexation of tanshinone IIA with 2-hydroxypropyl-beta-cyclodextrin: effect on aqueous solubility, dissolution rate, and intestinal absorption behavior in rats.
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.
Wang
Ling
L
West China Second University Hospital, Sichuan University, Chengdu, No. 17, Section 3, Southern Renmin Road, Chengdu 610041, PR China.
Jiang
Xuehua
X
Xu
Weijuan
W
Li
Chenrui
C
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D045784:Abietanes; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010539:Permeability; D010616:Phenanthrenes / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D045784:Abietanes; D004337:Drug Carriers; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D047392:beta-Cyclodextrins; C021751:tanshinone; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin