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Improvement of Bioavailability for Lovastatin using Self-microemulsifying Drug Delivery System

미세유화약물송달시스템을 이용한 로바스타틴의 생체이용률 향상

  • Yoon, Bok-Young (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Kang, Bok-Ki (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Jeung, Sang-Young (Biomaterials Laboratory, Korea Research Institute of Chemical Technology) ;
  • Lee, Young-Won (College of Veterinary Medicine, Chungnam National University) ;
  • Lee, Si-Beum (College of Pharmacy, Chungnam National University) ;
  • Hwang, Sung-Joo (College of Pharmacy, Chungnam National University) ;
  • Yuk, Soon-Hong (Department of Macromolecular Science, Hannam University) ;
  • Khang, Gil-Son (Department of Advanced Organic Materials Engineering, Chonbuk National University) ;
  • Lee, Hai-Bang (Biomaterials Laboratory, Korea Research Institute of Chemical Technology) ;
  • Cho, Sun-Hang (Biomaterials Laboratory, Korea Research Institute of Chemical Technology)
  • 윤복영 (전북대학교 유기신물질공학과) ;
  • 강복기 (전북대학교 유기신물질공학과) ;
  • 정상영 (한국화학연구원 생체의료고분자팀) ;
  • 이영원 (충남대학교 수의과대학) ;
  • 이시범 (충남대학교 약학대학) ;
  • 황성주 (충남대학교 약학대학) ;
  • 육순홍 (한남대학교 고분자공학과) ;
  • 강길선 (전북대학교 유기신물질공학과) ;
  • 이해방 (한국화학연구원 생체의료고분자팀) ;
  • 조선행 (한국화학연구원 생체의료고분자팀)
  • Published : 2002.12.20

Abstract

A self-microemulsifying drug delivery system (SMEDDS) was developed to increase the dissolution rate, solubility, and ultimately bioavailability of a poorly water soluble drug, lovastatin. SMEDDS was thε mixtures of oils, surfactants, and cosurfactants, which emulsify under conditions of gentle agitation, similar to those which would be encountered in the gastro-intestinal (GI) tract. Various types of self-emulsifying formulations were prepared using four types of oil (Capryol 90, Lauroglycol 90, Labrafil M 1944 CS and Labrafil M 2125), two surfactants (Cremophor EL and Tween 80), and three cosurfactants (Carbitol, PEG 400 and propylene glycol). Thε efficiency of emulsification was studied using a laser diffraction size analyzer to determine particle size distributions of the resultant emulsions. Optimized formulations selected for bioavailability assessment were Carpryol 90 (40%), Cremophor EL (30%) and Carbitol (30%). SMEDDS containing lovastatin (20 mg and 5 mg) were compared to a conventional lovastatin tablet $(Mevacor^{\circledR},\;20\;mg/tab)$ by the oral administration as prefilled hard gelatin capsules to fasted beagle dogs for in vivo study. The arεa under the serum concentration-time curve from time zero to the last measured time in serum, $AUC_{0{\rightarrow}24h}$, was significantly greater in SMEDDS, suggesting that bioavailability increase 130% and 192% by the SMEDDS, respectively. The self-emulsifying formulations of lovastatin afforded the improvement in absolute oral bioavailability relative to previous data of lovastatin tablet formulation. These data indicate the utility of dispersed self-emulsifying formulations for the oral delivery of lovastatin and potentially other poorly absorbed drugs.

Keywords

References

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