title: Bile salt/phospholipid mixed micelle precursor pellets prepared by fluid-bed coating.
abstract: Bile salt/phospholipid mixed micelles (MMs) are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing bile salt/phospholipid MM precursor (preMM) pellets with high oral bioavailability, using fluid-bed coating technology, was examined. In this study, fenofibrate (FB) and sodium deoxycholate (SDC) were used as the model drug and the bile salt, respectively. To prepare the MMs and to serve as the micellular carrier, a weight ratio of 4:6 was selected for the sodium deoxycholate/phospholipids based on the ternary phase diagram. Polyethylene glycol (PEG) 6000 was selected as the dispersion matrix for precipitation of the MMs onto pellets, since it can enhance the solubilizing ability of the MMs. Coating of the MMs onto the pellets using the fluid-bed coating technology was efficient and the pellets were spherical and intact. MMs could be easily reconstituted from preMM pellets in water. Although they existed in a crystalline state in the preMM pellets, FB could be encapsulated into the reconstituted MMs, and the MMs were redispersed better than solid dispersion pellets (FB:PEG = 1:3) and Lipanthyl®. The redispersibility of the preMM pellets increased with the increase of the FB/PEG/micellar carrier. PreMM pellets with a FB:PEG:micellar carrier ratio of 1:1.5:1.5 showed 284% and 145% bioavailability relative to Lipanthyl® and solid dispersion pellets (FB:PEG = 1:3), respectively. Fluid-bed coating technology has considerable potential for use in preparing sodium deoxycholate/phospholipid preMM pellets, with enhanced oral bioavailability for poorly water-soluble drugs.
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Shanghai, People's Republic of China.
authors: Fuxia
authors: F
authors: Dong
authors: Yunchang
authors: Y
authors: Xie
authors: Jianping
authors: J
authors: Qi
authors: Fuqiang
authors: F
authors: Hu
authors: Yi
authors: Y
authors: Lu
authors: Sanming
authors: S
authors: Li
authors: Wei
authors: W
authors: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D018592:Cross-Over Studies; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011345:Fenofibrate / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008823:Micelles; D010316:Particle Size; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D001647:Bile Acids and Salts; D004337:Drug Carriers; D008823:Micelles; D010743:Phospholipids; D003840:Deoxycholic Acid; D011345:Fenofibrate
keywords: bile salts; fluid-bed coating; mixed micelles; oral bioavailability; phospholipids
references: Int J Nanomedicine. 2011;6:795-805
references: 21589647
references: J Pharm Sci. 2009 Feb;98(2):665-75
references: 18543294
references: Nat Rev Drug Discov. 2007 Mar;6(3):231-48
references: 17330072
references: J Phys Chem B. 2008 Apr 3;112(13):3997-4008
references: 18335917
references: Planta Med. 2008 Feb;74(2):126-32
references: 18240100
references: Drug Discov Today Technol. 2012 Summer;9(2):e71-e174
references: 24064268
references: Eur J Pharm Sci. 2003 Feb;18(2):113-20
references: 12594003
references: J Pharm Sci. 2010 Mar;99(3):1336-45
references: 19743502
references: AAPS J. 2009 Dec;11(4):740-6
references: 19876745
references: J Pharm Pharmacol. 1988 Feb;40(2):85-8
references: 2897458
references: Drug Dev Ind Pharm. 1999 Apr;25(4):409-17
references: 10194595
references: Eur J Pharm Biopharm. 2006 Jan;62(1):3-16
references: 16129588
references: J Biomed Nanotechnol. 2012 Jun;8(3):515-21
references: 22764422
references: Eur J Pharm Biopharm. 2005 May;60(1):147-51
references: 15848066
references: Int J Pharm. 2010 Aug 16;395(1-2):272-80
references: 20580793
references: Int J Pharm. 2011 Dec 15;421(2):252-7
references: 22001534
references: J Drug Target. 2012 Aug;20(7):615-22
references: 22726209
references: Drug Deliv. 2005 Jan-Feb;12(1):35-9
references: 15801719
references: Clin Ther. 2004 Sep;26(9):1456-69
references: 15531008
references: Acta Pharmacol Sin. 2011 Jan;32(1):108-15
references: 21170082
references: Pharm Dev Technol. 2012 Mar-Apr;17(2):236-41
references: 21067338
references: Biochemistry. 1980 Feb 19;19(4):601-15
references: 7356951
references: Can J Physiol Pharmacol. 1993 Aug;71(8):531-55
references: 8306192
references: Atherosclerosis. 1994 Oct;110 Suppl:S45-8
references: 7857384
references: J Lipid Res. 1967 Nov;8(6):551-7
references: 6057484
references: Arch Pharm Res. 2010 Jun;33(6):911-7
references: 20607496
references: Adv Drug Deliv Rev. 2007 Jul 30;59(7):603-16
references: 17619064
references: Drugs. 2002;62(13):1909-44
references: 12215067
references: J Pharm Pharmacol. 2004 Jul;56(7):827-40
references: 15233860
references: J Gastroenterol Hepatol. 2008 Mar;23(3):430-6
references: 17868333
references: Eur J Pharm Biopharm. 2007 Aug;67(1):96-105
references: 17329087
references: Drugs. 1990 Aug;40(2):260-90
references: 2226216
references: Pharm Dev Technol. 2013 Feb;18(1):130-6
references: 22304703
references: Eur J Pharm Biopharm. 1998 Nov;46(3):361-7
references: 9885310
references: Chem Phys Lipids. 2005 May;135(1):93-104
references: 15854628
references: Biol Pharm Bull. 2003 Dec;26(12):1739-43
references: 14646182
references: Clin Pharmacokinet. 2006;45(4):425-32
references: 16584288