In situ formation of nanocrystals from a self-microemulsifying drug delivery system to enhance oral bioavailability of fenofibrate

Abstract

You-Meei Lin1, Jui-Yu Wu2, Ying-Chen Chen3, Yu-Der Su3, Wen-Tin Ke3, Hsiu-O Ho31Department of Pharmacy, Shuang Ho Hospital, 2Department of Biochemistry, School of Medicine, 3School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROCObjectives: 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.Conclusion: SMEDDS, consisting of Myritol 318 and TPGS combined with Tween 80 at 4:1, was able to enhance the oral bioavailability of FFB.Keywords: SMEDDS, fenofibrate, microemulsion, dissolution, TPGS