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

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• 作者：Dong Woo Yeom^a ; ^{yeompd@naver.com" class="auth_mail" title="E-mail the corresponding author} ; Ho Yong Son^a ; ^{lakers0204@naver.com" class="auth_mail" title="E-mail the corresponding author} ; Jin Han Kim^a ; ^{jinhan8910@daum.net" class="auth_mail" title="E-mail the corresponding author} ; Sung Rae Kim^a ; ^{kimsrkr@naver.com" class="auth_mail" title="E-mail the corresponding author} ; Sang Gon Lee^a ; ^{idealgon@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; She Hyon Song^b ; ^{208058@daewonpharm.com" class="auth_mail" title="E-mail the corresponding author} ; Bo Ram Chae^b ; ^{hifyram@daewonpharm.com" class="auth_mail" title="E-mail the corresponding author} ; Young Wook Choi^a ; ^{ywchoi@cau.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Atorvastatin ; SMEDDS ; Solidified SMEDDS ; Solid carrier ; Sylysia® ; 350 ; Mannitol
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：506
• 期：1-2
• 页码：302-311
• 全文大小：1618 K

文摘

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^® MCM (oil), Tween^® 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^® 350 (S) and Aerosil^® 200 (A) as water-insoluble carriers. Maximum solidifying capacities (SC_max) 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° 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^® 350 (S(S)-SMEDDS) or Aerosil^® 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.