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Hydration of an amphiphilic excipient, Gelucire (R) 44/14

Svensson, Anna LU ; Neves, C and Cabane, B (2004) In International Journal of Pharmaceutics 281(1-2). p.107-118
Abstract
The incorporation of drugs into Gelucires has been reported to increase the dissolution rate of poorly soluble drugs, often leading to improved drug bioavailability. In pharmaceutical applications, it is important to know how the excipient interacts with the drug, and how the mixture behaves during manufacturing, storage as well as during administration. The uptake of water by an amphiphilic excipient, Gelucire(R) 44/14, has been investigated in two ways: storage in humid air and addition of liquid water. During exposure to humid air, the uptake goes in stages that correspond to the dissolution of the components of the excipient, starting with the most hydrophilic ones: glycerol, then polyethylene glycol (PEG), PEG esters (PEG monolaurate... (More)
The incorporation of drugs into Gelucires has been reported to increase the dissolution rate of poorly soluble drugs, often leading to improved drug bioavailability. In pharmaceutical applications, it is important to know how the excipient interacts with the drug, and how the mixture behaves during manufacturing, storage as well as during administration. The uptake of water by an amphiphilic excipient, Gelucire(R) 44/14, has been investigated in two ways: storage in humid air and addition of liquid water. During exposure to humid air, the uptake goes in stages that correspond to the dissolution of the components of the excipient, starting with the most hydrophilic ones: glycerol, then polyethylene glycol (PEG), PEG esters (PEG monolaurate and PEG dilaurate), and finally glycerides (trilaurin). At each stage, the remaining: crystals are in equilibrium with an interstitial solution made of water and the dissolved components. In this range of hydrations, the total uptake is close to the sum of the equilibrium hydrations of the components. In the pharmaceutical formulation, the active ingredient could dissolve in the liquid phase. At larger hydrations obtained through addition of liquid water, the state of Gelucire(R) 44/14 differs from those of its components. Gelucire(R) 44/14 forms a lamellar phase and this phase melts at 30degreesC whereas the pure PEG esters form hexagonal and cubic mesophases. The cubic mesophases do not melt until the temperature exceeds 40degreesC. At body temperature, all crystals in Gelucire(R) 44/14 melt to an isotropic fluid as soon as the total water content exceeds 5%. Therefore the formulation of amphiphilic excipients can be optimized to avoid the formation of mesophases that impede dissolution of the excipient at body temperature. (C) 2004 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gelucire® 44/14, Phase diagram, Hydration, Dissolution, Mesophases, PEG esters, DVS, SAXS, WAXS
in
International Journal of Pharmaceutics
volume
281
issue
1-2
pages
107 - 118
publisher
Elsevier
external identifiers
  • pmid:15288348
  • wos:000223499300011
  • scopus:3543054733
ISSN
1873-3476
DOI
10.1016/j.ijpharm.2004.06.005
language
English
LU publication?
yes
id
b323cf65-3a61-42d8-a728-bce74d0441a3 (old id 154065)
date added to LUP
2007-07-12 12:13:33
date last changed
2017-01-29 03:32:36
@article{b323cf65-3a61-42d8-a728-bce74d0441a3,
  abstract     = {The incorporation of drugs into Gelucires has been reported to increase the dissolution rate of poorly soluble drugs, often leading to improved drug bioavailability. In pharmaceutical applications, it is important to know how the excipient interacts with the drug, and how the mixture behaves during manufacturing, storage as well as during administration. The uptake of water by an amphiphilic excipient, Gelucire(R) 44/14, has been investigated in two ways: storage in humid air and addition of liquid water. During exposure to humid air, the uptake goes in stages that correspond to the dissolution of the components of the excipient, starting with the most hydrophilic ones: glycerol, then polyethylene glycol (PEG), PEG esters (PEG monolaurate and PEG dilaurate), and finally glycerides (trilaurin). At each stage, the remaining: crystals are in equilibrium with an interstitial solution made of water and the dissolved components. In this range of hydrations, the total uptake is close to the sum of the equilibrium hydrations of the components. In the pharmaceutical formulation, the active ingredient could dissolve in the liquid phase. At larger hydrations obtained through addition of liquid water, the state of Gelucire(R) 44/14 differs from those of its components. Gelucire(R) 44/14 forms a lamellar phase and this phase melts at 30degreesC whereas the pure PEG esters form hexagonal and cubic mesophases. The cubic mesophases do not melt until the temperature exceeds 40degreesC. At body temperature, all crystals in Gelucire(R) 44/14 melt to an isotropic fluid as soon as the total water content exceeds 5%. Therefore the formulation of amphiphilic excipients can be optimized to avoid the formation of mesophases that impede dissolution of the excipient at body temperature. (C) 2004 Elsevier B.V. All rights reserved.},
  author       = {Svensson, Anna and Neves, C and Cabane, B},
  issn         = {1873-3476},
  keyword      = {Gelucire® 44/14,Phase diagram,Hydration,Dissolution,Mesophases,PEG esters,DVS,SAXS,WAXS},
  language     = {eng},
  number       = {1-2},
  pages        = {107--118},
  publisher    = {Elsevier},
  series       = {International Journal of Pharmaceutics},
  title        = {Hydration of an amphiphilic excipient, Gelucire (R) 44/14},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2004.06.005},
  volume       = {281},
  year         = {2004},
}