Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium

Title
Enhanced Solubility and Bioavailability of Sibutramine Base by Solid Dispersion System with Aqueous Medium
Author(s)
최한곤용철순우종수이동훈장기영오동훈서윤기김영란김종오강원구[강원구]이만형[이만형]배경진[배경진]오유경[오유경]지준필[지준필]박영준[박영준]
Keywords
SPRAY-DRYING TECHNIQUE; DRUG; RELEASE; ITRACONAZOLE; IBUPROFEN; PHARMACOKINETICS; FORMULATION; POLYMERS; TABLETS; OBESITY
Issue Date
201002
Publisher
PHARMACEUTICAL SOC JAPAN
Citation
BIOLOGICAL & PHARMACEUTICAL BULLETIN, v.33, no.2, pp.279 - 284
Abstract
To develop a novel sibutramine base-loaded solid dispersion with improved solubility bioavailability, various solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil (R)). The sibutramine base-loaded solid dispersion gave two type forms. Like conventional solid dispersion system, one type appeared as a spherical shape with smooth surface, as the carriers and drug with relatively low melting point were soluble in water and formed it. The other appeared as an irregular form with relatively rough surface. Unlike conventional solid dispersion system, this type changed no crystalline form of drug. Our results suggested that this type was formed by, attaching hydrophilic carriers to the surface of drug without crystal change, resulting from changing the hydrophobic drug to hydrophilic form. The sibutramine-loaded solid dispersion at the weight ratio of sibutramine base/HPMC/poloxamer/citric acid of 5/3/3/0.2 gave the maximum drug solubility of about 3 mg/ml. Furthermore, it showed the similar plasma concentration, area under the curve (AUC) and C-max of parent drug, metabolite I and II to the commercial product, indicating that it might give the similar drug efficacy compared to the sibutramine hydrochloride monohydrate-loaded commercial product in rats. Thus, this solid dispersion system would be useful to deliver poorly water-soluble sibutramine base with enhanced bioavailability.
URI
http://hdl.handle.net/YU.REPOSITORY/22938
ISSN
0918-6158
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약학대학 > 약학부 > Articles
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