title: Enhanced oral bioavailability and controlled release of dutasteride by a novel dry elixir.
abstract: To develop a solid dosage form of dutasteride for improving its oral bioavailability, a novel dry elixir (DE) system was fabricated. DEs incorporating dextrin and/or xanthan gum were prepared using spray-drying and evaluated by morphology, ethanol content, crystallinity, dissolution and oral bioavailability. DEs were spherical with a smooth surface and had an average particle size of 20-25 μm. The ethanol content could be easily varied by controlling the spray-drying temperature. The dissolution profiles of dutasteride from each DE proved to be much faster than that of dutasteride powder due to the amorphous state and a high amount of incorporated ethanol. In particular, the pharmacokinetic profiles of dutasteride were significantly altered depending on the proportions of dextrin and xanthan gum. Blood concentrations of dutasteride from DE formulations were similar to those of market products and much greater than those of native dutasteride. Interestingly, the dissolution and pharmacokinetic profiles were easily controlled by changing the ratio of dextrin to xanthan gum. The data suggests that a DE using dextrin and/or xanthan gum could provide an applicable solid dosage form to improve the dissolution and bio-availability of dutasteride as well as to modulate its pharmacokinetics.
authors.affiliation: College of Pharmacy, The Catholic University of Korea, Bucheon, Gyeonggi 420-743, Republic of Korea.
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Jang
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Euichaul
authors.initials: E
authors.lastname: Oh
authors.forename: Eunmi
authors.initials: E
authors.lastname: Ban
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001378:Azasteroids / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002853:Chromatography, Liquid; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003912:Dextrins / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D000068538:Dutasteride; D000431:Ethanol / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D013696:Temperature; D064804:Urological Agents / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D001378:Azasteroids; D003692:Delayed-Action Preparations; D003912:Dextrins; D004337:Drug Carriers; D011135:Polysaccharides, Bacterial; D011208:Powders; D064804:Urological Agents; D000431:Ethanol; D000068538:Dutasteride; C002563:xanthan gum
keywords: Dutasteride; dissolution; dry elixir; oral bioavailability; xanthan gum