Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Development of Self-microemulsifying Drug Delivery System for Enhancing the Bioavailability of Atorvastatin

  • Jin, Shun-Ji (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Cho, Won-Kyung (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Park, Hee-Jun (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Cha, Kwang-Ho (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Park, Jun-Sung (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Koo, Ja-Seong (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Wang, Hun-Sik (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Kim, Jeong-Soo (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Kim, Min-Soo (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University) ;
  • Hwang, Sung-Joo (Center for Nanotechnology-based New Drug Dosage Form, College of Pharmacy, Chungnam National University)
  • Received : 2011.03.25
  • Accepted : 2011.03.31
  • Published : 2011.04.20
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Abstract

The objective of the study was to prepare self-microeulsifying drug delivery system (SMEDDS) incorporating atorvastatin calcium and evaluate its properties and oral bioavailability. Solubility of atorvastatin in various vehicles was determined. Pseudo-ternary phase diagrams were constructed to identify the good self-emulsification region. The droplet size distributions of the resultant emulsions were determined by dynamic light scattering measurement. The mean droplet size of chosen formulation (20% ethyl oleate, 40% tween-80, 40% Carbitol$^{(R)}$) was $23.4{\pm}1.3$ nm. The SMEDDS incorporating atorvastatin calcium appeared to be associated with better performance in dissolution and pharmacokinetic studies, compared with raw atorvastatin calcium. In dissolution test, the release percentage of atorvastatin from SMEDDS mixture could rapidly reach more than 95% within 3 min. Oral $AUC_{0{\rightarrow}8hr}$ values in SD rats was $1994{\pm}335\;ng{\cdot}hr/mL$, which significantly increased (P<0.05) compared with raw atorvastatin calcium. The SMEDDS formulation was relatively stable when stored at $4^{\circ}C$ during 3 months. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin, by the oral route.

Keywords

References

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