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Structural development of self nano emulsifying drug delivery systems (SNEDDS) during In vitro lipid digestion monitored by small-angle x-ray scattering

Fatouros, Dimitrios G.; Deen, G. Roshan; Arleth, Lise; Bergenståhl, Björn LU ; Nielsen, Flemming Seier; Pedersen, Jan Skov and Mullertz, Anette (2007) In Pharmaceutical Research 24(10). p.1844-1853
Abstract
Purpose. To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine. Materials and Methods. Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble drugs. Results. The data revealed... (More)
Purpose. To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine. Materials and Methods. Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble drugs. Results. The data revealed that a lamellar phase forms immediately after initiation of lipolysis, whereas a hexagonal phase is formed after 60 min. The change of the relative amounts of these phases clearly demonstrates that lipolysis is a dynamic process. The formation of these phases is driven by the lipase which continuously hydrolyzes triglycerides from the oil-cores of the nanoemulsion droplets into mono- and diglycerides and fatty acids. We propose that this change of the over-all composition of the intestinal fluid with increased fraction of hydrolyzed nanoemulsion induces a change in the composition and effective critical packing parameter of the amphiphilic molecules, which determines the phase behavior of the system. Control experiments (only the digestion medium) or the surfactant (Cremophor RH 40) revealed the formation of a lamellar phase demonstrating that the hexagonal phase is due to the hydrolysis of the SNEDDS formulation. Conclusion. The current results demonstrate that SAXS measurements combined with the in vitro dynamic lipolysis model may be used to elucidate the processes encountered during the digestion of lipid-based formulations of poorly soluble drugs for oral drug delivery. Thus the combined methods may act as an efficient screening tool. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
delivery, SAXS, oral, nano-emulsions, liquid crystals, Cryo-TEM, in vitro digestion
in
Pharmaceutical Research
volume
24
issue
10
pages
1844 - 1853
publisher
Springer
external identifiers
  • wos:000249407900005
  • scopus:34548567075
ISSN
1573-904X
DOI
10.1007/s11095-007-9304-6
language
English
LU publication?
yes
id
5052122d-a3b9-4f05-97ba-c1e1087179c2 (old id 687650)
date added to LUP
2007-12-10 11:34:07
date last changed
2017-09-24 03:47:17
@article{5052122d-a3b9-4f05-97ba-c1e1087179c2,
  abstract     = {Purpose. To investigate the structural development of the colloid phases generated during lipolysis of a lipid-based formulation in an in vitro lipolysis model, which simulates digestion in the small intestine. Materials and Methods. Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model which accurately reproduces the solubilizing environment in the gastrointestinal tract and simulates gastrointestinal lipid digestion through the use of bile and pancreatic extracts. The combined method was used to follow the intermediate digestion products of a self nano emulsified drug delivery system (SNEDDS) under fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble drugs. Results. The data revealed that a lamellar phase forms immediately after initiation of lipolysis, whereas a hexagonal phase is formed after 60 min. The change of the relative amounts of these phases clearly demonstrates that lipolysis is a dynamic process. The formation of these phases is driven by the lipase which continuously hydrolyzes triglycerides from the oil-cores of the nanoemulsion droplets into mono- and diglycerides and fatty acids. We propose that this change of the over-all composition of the intestinal fluid with increased fraction of hydrolyzed nanoemulsion induces a change in the composition and effective critical packing parameter of the amphiphilic molecules, which determines the phase behavior of the system. Control experiments (only the digestion medium) or the surfactant (Cremophor RH 40) revealed the formation of a lamellar phase demonstrating that the hexagonal phase is due to the hydrolysis of the SNEDDS formulation. Conclusion. The current results demonstrate that SAXS measurements combined with the in vitro dynamic lipolysis model may be used to elucidate the processes encountered during the digestion of lipid-based formulations of poorly soluble drugs for oral drug delivery. Thus the combined methods may act as an efficient screening tool.},
  author       = {Fatouros, Dimitrios G. and Deen, G. Roshan and Arleth, Lise and Bergenståhl, Björn and Nielsen, Flemming Seier and Pedersen, Jan Skov and Mullertz, Anette},
  issn         = {1573-904X},
  keyword      = {delivery,SAXS,oral,nano-emulsions,liquid crystals,Cryo-TEM,in vitro digestion},
  language     = {eng},
  number       = {10},
  pages        = {1844--1853},
  publisher    = {Springer},
  series       = {Pharmaceutical Research},
  title        = {Structural development of self nano emulsifying drug delivery systems (SNEDDS) during In vitro lipid digestion monitored by small-angle x-ray scattering},
  url          = {http://dx.doi.org/10.1007/s11095-007-9304-6},
  volume       = {24},
  year         = {2007},
}