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KMID : 0370220120560030164
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Yakhak Hoeji
2012 Volume.56 No. 3 p.164 ~ p.172
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Enhanced Dissolution and Duodenal Permeation of Atorvastatin Calcium Using Bile Salt and 2-Hydroxypropyl--Cyclodextrin
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Choi Ji-Won
Chun In-Koo
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Abstract
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This study was aimed to increase the solubility, dissolution and permeation rates of atorvastatin calcium (ATC) using bile salt and/or 2-hydroxypropyl--cyclodextrin (). From solubility studies, sodium deoxycholate (SDC) among bile salts studied was found to have the highest solubilizing effect on ATC ( mg/ml), and the order of increasing solubility was SDC>sod. cholate>sod. glycocholate>sod. taurodeoxycholate>sod. taurocholate>conjugated bile acid. ATC solid dispersions were prepared at various ratios of drug to SDC and/or , and evaluated by differential scanning calorimetry (DSC), dissolution studies and dissolution-permeation studies. DSC curves showed amorphous state of ATC in the physical mixture and solid dispersion. Dissolution rates of ATC-SDC solid dispersions and physical mixture were markedly increased at pH 6.8, but decreased at pH 1.2 with greater proportions of SDC due to the precipitation of SDC, compared with that of drug alone. On the other hand, dissolution rates of ATC- solid dispersion and physical mixture at pH 1.2 were varied with the ratio of drug to carriers. From duodenal permeation studies, it was found that fluxes of ATC (donor dose: 0.5 mg/3.5 ml) in the presence of 25 mM sodium glycocholate, SDC, sod. cholate and sod. taurocholate , , and , respectively) were enhanced, compared with drug alone (). In the dissolution-permeation studies, 1 : 9 : 10 (w/w) ATC-SDC- solid dispersion increased the flux 2.2 times, compared with 1 : 5 : 4 (w/w) ATC-lactose-corn starch mixture as control. In conclusion, solid dispersions with bile salt and were found to be an effective means for increasing the dissolution and permeation rates of ATC.
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KEYWORD
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atorvastatin calcium, bile salt, 2-hydroxypropyl--cyclodextrin, dissolution, duodenal permeation, enhancement
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