Development of a solidified self-microemulsifying drug delivery system (S-SMEDDS) for atorvastatin calcium with improved dissolution and bioavailability

作者：Yeom Dong Woo; Son Ho Yong; Kim Jin Han; Kim Sung Rae; Lee Sang Gon; Song She Hyon; Chae Bo Ram; Choi Young Wook^*

来源：International Journal of Pharmaceutics, 2016, 506(1-2): 302-311.

DOI：10.1016/j.ijpharm.2016.04.059

• Atorvastatin
• SMEDDS
• Solidified SMEDDS
• Solid carrier
• Sylysia (R) 350
• Mannitol

To improve the dissolution and oral bioavailability (BA) of atorvastatin calcium (ATV), we previously introduced an optimized self-microemulsifying drug delivery system (SMEDDS) using Capmul (R) MCM (oil), Tween (R) 20 (surfactant), and tetraglycol (cosurfactant). In this study, various solid carriers were employed to develop a solidified SMEDDS (S-SMEDDS): mannitol (M) and lactose (L) as water-soluble carriers, and Sylysia (R) 350 (S) and Aerosil (R) 200 (A) as water-insoluble carriers. Maximum solidifying capacities (SCmax) of water-insoluble carriers were significantly greater than those of water-soluble carriers were. The resultant powders were free flowing with an angle of repose <40 degrees and Carr's index 5-20%, regardless of the solid carrier types. S-SMEDDS with mannitol (S(M)-SMEDDS) or lactose (S(L)SMEDDS) had a smaller droplet size and greater dissolution than S-SMEDDS with Sylysia (R) 350 (S(S)SMEDDS) or Aerosil (R) 200 (S(A)-SMEDDS). Following oral administration of various formulations to rats at a dose equivalent to 25 mg/kg of ATV, plasma drug levels were measured by LC-MS/MS. The relative BAs (RBAs) of SMEDDS, S(M)-SMEDDS, and S(S)-SMEDDS were 345%, 216%, and 160%, respectively, compared to that of ATV suspension. Additionally, at a reduced dose of ATV equivalent to 5 mg/kg, the RBAs of S(M)-SMEDDS and S(S)-SMEDDS compared to that of SMEDDS were 101% and 65%, respectively. These results suggest that S(M)-SEMDDS offers great potential for the development of solid dosage forms with improved oral absorption of drugs with poor water solubility.

• 出版日期2016-6-15