Characterization, stability, and pharmacokinetics of sibutramine/β-cyclodextrin inclusion complex베타-시클로덱스트린과 시부트라민 포접체의 특성분석, 안정성 및 약력학

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 631
  • Download : 0
The sibutramine/β-cyclodextrin (β-CD) inclusion complex was prepared through the solution method as a potential stabilizing carrier for unstable sibutramine base. The formation of inclusion complex between sibutramine and β-CD was characterized via differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and 1H nuclear magnetic resonance (NMR). From the NMR spectra and the assay for the optimized sibutramine/β-CD inclusion complex, the molar ratio of sibutramine base and β-CD in inclusion complex was expected to be 1:2. The thermal and photochemical stability of sibutramine was effectively increased through its complexation with β-CD comparable to stable salt form of sibutramine hydrochloride monohydrate. Furthermore, molecular modeling explained that the host-guest size match and the hydrogen bond interaction between sibutramine and β-CD or two β-CDs played two major roles in the formation of tight inclusion complex and stabilization of sibutramine, which kept the labile N,N-dimethyl group of sibutramine from being exposed to degradable environments. The present study suggested that the inclusion complexation with β-CD is a promising method to develop a sibutramine base-loaded product with improved stability. The oral dosage form of sibutramine/β-CD complex pharmaceutically equivalent to reference drug, Reductil® was developed in this study. The solubility of sibutramine showed that the main strategy for formulation development of sibutramine/β-CD complex was to increase solubility or dissolution rate in weak acidic condition. From the compatibility study, major excipients such as diluents, lubricants, disintegrants and a solubilizer was selected for formulation development. The formulation was optimized for the kind and amount of compatible excipients via dissolution testing. The decisive excipient influencing dissolution rate of sibutramine in weak acidic condition was lactose monohydrate and citric acid as diluent and pH modifier, respectiv...
Advisors
Cho, Byung-Kwanresearcher조병관Nam, Yoon-Sung남윤성
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2012
Identifier
511409/325007  / 020035898
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2012.8, [ ix, 109 p. ]

Keywords

cyclodextrin; inclusion; stability; sibutramine; 베타-시클로덱스트린; 포접; 안정성; 처방; 시부트라민; formulation

URI
http://hdl.handle.net/10203/179828
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=511409&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
Files in This Item
There are no files associated with this item.

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0