Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Biopharmaceutical Evaluation of a Solid Dispersion System Containing Sibutramine Freebase

  • Lee, Min-Suk (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Chang, Hee-Chul (Pharmaceutical Research Institute, Daewoong Pharmaceutical Co., Ltd.) ;
  • Kim, Taewan (Pharmaceutical Research Institute, Daewoong Pharmaceutical Co., Ltd.) ;
  • Park, Jung-Hwa (Pharmaceutical Research Institute, Daewoong Pharmaceutical Co., Ltd.) ;
  • Lee, Bong-Sang (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Kim, Sung-Hee (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Kim, Do-Hwan (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Kim, Bo-Gyun (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Oh, Seong-Tae (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Kang, Myung-Joo (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Park, Jong-Hyeok (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Lee, Jaehwi (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University) ;
  • Choi, Young-Wook (Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University)
  • Published : 2008.04.20
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Abstract

To increase the solubility of sibutramine freebase, the solid dispersion was prepared using a fluid-bed granulator. The solid dispersion containing sibutramine freebase was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). After filling the sibutramine solid dispersion in the gelatin hard capsule, we performed in vitro dissolution test, the stability test under accelerated conditions and pharmacokinetic study in beagle dogs. The DSC and XRD data showed that sibutramine solid dispersion would be amorphous state. The dissolution rate of sibutramine solid dispersion was significantly increased about 70% than sibutramine freebase. The stability of sibutramine solid dispersion capsules was equivalent or above to commercial product of sibutramine. In beagle dogs, the sibutramine solid dispersion showed equivalent pharmacokinetic behavior with commercial product of sibutramine hydrochloride. In conclusion, the solid dispersion system provided a possible way to overcome the low solubility of sibutramine freebase, and the sibutramine solid dispersion can be a bioequivalent with the commercial product in humans.

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References

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