Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water soluble drugs I. Phase behaviour in physiologically-relevant media.
OBJECTIVE
The potential utility of liquid crystalline lipid-based formulations in oral drug delivery is expected to depend critically on their structure formation and stability in gastrointestinal fluids. The phase behaviour of lipid-based liquid crystals formed by phytantriol and glyceryl monooleate, known to form a bicontinuous cubic phase in excess water, was therefore assessed in physiologically-relevant simulated gastrointestinal media.


METHODS
Fixed composition phase studies, crossed polarised light microscopy (CPLM) and small angle X-ray scattering (SAXS) were used to determine the phase structures formed in phosphate-buffered saline, simulated gastric and intestinal fluids in the presence of model poorly water soluble drugs cinnarizine, diazepam and vitamin E acetate.


RESULTS
The phase behaviour of phytantriol in phosphate-buffered saline was very similar to that in water. Increasing concentrations of bile components (bile salts and phospholipids) caused an increase in the lattice parameter of the cubic phase structure for both lipids. Incorporation of cinnarizine and diazepam did not influence the phase behaviour of the phytantriol- or glyceryl monooleate-based systems at physiological temperatures; however, an inverse hexagonal phase formed on incorporation of vitamin E acetate.


CONCLUSIONS
Phytantriol and glyceryl monooleate have the potential to form stable cubic phase liquid crystalline delivery systems in the gastrointestinal tract. In-vivo studies to assess their sustained-release behaviour are warranted.
Nguyen
Tri-Hung
TH
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Hanley
Tracey
T
Porter
Christopher J H
CJ
Larson
Ian
I
Boyd
Ben J
BJ
D001647:Bile Acids and Salts; D002626:Chemistry, Pharmaceutical; D002936:Cinnarizine / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D003975:Diazepam / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005233:Fatty Alcohols / Q000737:chemistry*; D005750:Gastric Juice; D041981:Gastrointestinal Tract; D005989:Glycerides / Q000737:chemistry*; D007422:Intestines; D050866:Liquid Crystals; D010743:Phospholipids; D012965:Sodium Chloride; D012995:Solubility; D014810:Vitamin E / Q000737:chemistry; D014867:Water / Q000737:chemistry
D001647:Bile Acids and Salts; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005233:Fatty Alcohols; D005989:Glycerides; D010743:Phospholipids; D014867:Water; D014810:Vitamin E; D002936:Cinnarizine; D012965:Sodium Chloride; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; C005953:monoolein; D003975:Diazepam