title: In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate.
abstract: OBJECTIVE
  In situ formation of nanocrystals and dissolution profiles of fenofibrate (FFB) from a self-microemulsifying drug delivery system (SMEDDS) were characterized.
  
  
  METHODS
  SMEDDS formulated with Myritol and surfactant mixture (Smix) of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and either Tween 20 (A, C, E, G, M, S, N, T, O) or Tween 80 (B, D, F, H, P, U, Q, V, R) at various oil/Smix ratios (Group I: A and B of 0.42, C and D of 0.25, E and F of 0.11; Group II: G and H of 1.38, M and P of 1.11, S and U of 0.9, N and Q of 0.73, T and V of 0.58, and O and R of 0.46) and water contents (1: 9.5%, 2: 5.0%, 3: 0.0%, G-V: 4.5%). Their dissolutions were conducted at different rotation speeds. Two optimal SMEDDSs containing Tween 80(B2) or a higher oil/Smix ratio(Q) and B2(solution) were selected for pharmacokinetic study.
  
  
  RESULTS
  FFB particles formed within the nanosize range from Group I gradually increased with time but decreased with increasing stirring rates. However, the mean size of FFB formed by B series was as low as 200 nm, which was smaller than that of A series at three stirring rates. The release rate from both groups obviously increased with increasing stirring rate. However, incomplete release was observed for S and N in Tween 20 series, whereas a faster release rate and complete release were observed for Tween 80 series with an insignificant difference among them. Results of pharmacokinetic study demonstrated that the highest-ranked area under the curve and Cmax values were for Q(SMEDDS) and B2(solution), respectively. The relative bioavailability of Q(SMEDDS) with respect to Tricor was enhanced by about 1.14-1.22-fold.
  
  
  CONCLUSIONS
  SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB.
authors.affiliation: Department of Pharmacy, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan, ROC.
authors.forename: You-Meei
authors.initials: YM
authors.lastname: Lin
authors.forename: Jui-Yu
authors.initials: JY
authors.lastname: Wu
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-Der
authors.initials: YD
authors.lastname: Su
authors.forename: Wen-Tin
authors.initials: WT
authors.lastname: Ke
authors.forename: Hsiu-O
authors.initials: HO
authors.lastname: Ho
authors.forename: Ming-Thau
authors.initials: MT
authors.lastname: Sheu
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D019540:Area Under Curve; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D011345:Fenofibrate / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D011136:Polysorbates; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D011345:Fenofibrate
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