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Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium.
Biol Pharm Bull. 2010; 33(2):279-84.BP

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). 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.

Authors+Show Affiliations

College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyongsan 712-749, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20118553

Citation

Li, Dong Xun, et al. "Enhanced Solubility and Bioavailability of Sibutramine Base By Solid Dispersion System With Aqueous Medium." Biological & Pharmaceutical Bulletin, vol. 33, no. 2, 2010, pp. 279-84.
Li DX, Jang KY, Kang W, et al. Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium. Biol Pharm Bull. 2010;33(2):279-84.
Li, D. X., Jang, K. Y., Kang, W., Bae, K., Lee, M. H., Oh, Y. K., Jee, J. P., Park, Y. J., Oh, D. H., Seo, Y. G., Kim, Y. R., Kim, J. O., Woo, J. S., Yong, C. S., & Choi, H. G. (2010). Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium. Biological & Pharmaceutical Bulletin, 33(2), 279-84.
Li DX, et al. Enhanced Solubility and Bioavailability of Sibutramine Base By Solid Dispersion System With Aqueous Medium. Biol Pharm Bull. 2010;33(2):279-84. PubMed PMID: 20118553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium. AU - Li,Dong Xun, AU - Jang,Ki-Young, AU - Kang,Wonku, AU - Bae,Kyoungjin, AU - Lee,Mann Hyung, AU - Oh,Yu-Kyoung, AU - Jee,Jun-Pil, AU - Park,Young-Joon, AU - Oh,Dong Hoon, AU - Seo,Youn Gee, AU - Kim,Young Ran, AU - Kim,Jong Oh, AU - Woo,Jong Soo, AU - Yong,Chul Soon, AU - Choi,Han-Gon, PY - 2010/2/2/entrez PY - 2010/2/2/pubmed PY - 2010/9/4/medline SP - 279 EP - 84 JF - Biological & pharmaceutical bulletin JO - Biol Pharm Bull VL - 33 IS - 2 N2 - 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). 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. SN - 1347-5215 UR - https://www.unboundmedicine.com/medline/citation/20118553/Enhanced_solubility_and_bioavailability_of_sibutramine_base_by_solid_dispersion_system_with_aqueous_medium_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/bpb/33.279?from=PubMed DB - PRIME DP - Unbound Medicine ER -