title: Development of a solidified self-microemulsifying drug delivery system (S-SMEDDS) for atorvastatin calcium with improved dissolution and bioavailability.
abstract: 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 (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° 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 25mg/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 5mg/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.
authors.affiliation: College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: yeompd@naver.com.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Yeom
authors.affiliation: College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: lakers0204@naver.com.
authors.forename: Ho Yong
authors.initials: HY
authors.lastname: Son
authors.affiliation: College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: jinhan8910@daum.net.
authors.forename: Jin Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: kimsrkr@naver.com.
authors.forename: Sung Rae
authors.initials: SR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: idealgon@gmail.com.
authors.forename: Sang Gon
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Daewon Pharm. Co., Ltd., 520 Cheonhodae-ro, Gwangjin-gu, Seoul 04994, Republic of Korea. Electronic address: 208058@daewonpharm.com.
authors.forename: She Hyon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Daewon Pharm. Co., Ltd., 520 Cheonhodae-ro, Gwangjin-gu, Seoul 04994, Republic of Korea. Electronic address: hifyram@daewonpharm.com.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Chae
authors.affiliation: College of Pharmacy, Chung-Ang University, 84 Heuksuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: ywchoi@cau.ac.kr.
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000069059:Atorvastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D000924:Anticholesteremic Agents; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; D000069059:Atorvastatin
keywords: Atorvastatin; Mannitol; SMEDDS; Solid carrier; Solidified SMEDDS; Sylysia(®) 350