Investigation of the improved effects of 2-hydroxypropyl-beta-cyclodextrin on solubility, dissolution rate, and intestinal absorptive profile of tanshinone IIA in rats.
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.
Wang
Ling
L
Institution of Clinical Pharmacological, West China Second University Hospital, Sichuan University, Chengdu, P.R. China.
Jiang
Xuehua
X
Li
Chenrui
C
Ren
Jing
J
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D045784:Abietanes; D000818:Animals; D004355:Drug Stability; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D010616:Phenanthrenes / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
D045784:Abietanes; D004365:Drugs, Chinese Herbal; D005079:Excipients; D010616:Phenanthrenes; D047392:beta-Cyclodextrins; C021751:tanshinone; D000073738:2-Hydroxypropyl-beta-cyclodextrin