TY - JOUR
T1 - Nanostructured reverse hexagonal liquid crystals sustain plasma concentrations for a poorly water-soluble drug after oral administration
AU - Nguyen, Tri Hung
AU - Hanley, Tracey
AU - Porter, Christopher J H
AU - Boyd, Benjamin
PY - 2011/12
Y1 - 2011/12
N2 - Reverse hexagonal (H 2) liquid crystals formed from selachyl alcohol were demonstrated to sustain the absorption of the poorly water-soluble drug cinnarizine (CZ) after oral administration to rats. When CZ was administered as a bolus lipid solution in selachyl alcohol, the T max was observed to be 23.5 ± 5.9 h, significantly longer than the control suspension (1 h). Administration of selachyl alcohol as dispersed nanoparticles (hexosomes) also resulted in a sustained plasma profile, with drug concentrations maintained from 20 to 40 ng/mL over the first 24 h after administration. Sustained absorption of CZ from the selachyl alcohol hexosomes led to a significant enhancement (p <0.05) in oral bioavailability (F% = 17%) compared to the control CZ suspension (9%). Analysis of selachyl alcohol hexosomes using small-angle x-ray scattering indicated that neither the presence of CZ (7 mg/g) nor simulated intestinal fluid altered the H 2 nanostructure. Selachyl alcohol is not susceptible to digestion. Prolonged absorption from the selachyl alcohol-based H 2 systems was attributed to the non-digestible nature of the lipid, similar to non-digestible phytantriol cubic (V 2) systems previously reported. Furthermore, the likely presence of non-sink conditions in the gastric compartment provides a drug reservoir requiring gastric emptying to stimulate drug release from the formulation. This study highlights the potential use of non-digestible liquid crystalline systems generally and nanostructured liquid crystalline particles in particular as novel sustained oral drug delivery systems.
AB - Reverse hexagonal (H 2) liquid crystals formed from selachyl alcohol were demonstrated to sustain the absorption of the poorly water-soluble drug cinnarizine (CZ) after oral administration to rats. When CZ was administered as a bolus lipid solution in selachyl alcohol, the T max was observed to be 23.5 ± 5.9 h, significantly longer than the control suspension (1 h). Administration of selachyl alcohol as dispersed nanoparticles (hexosomes) also resulted in a sustained plasma profile, with drug concentrations maintained from 20 to 40 ng/mL over the first 24 h after administration. Sustained absorption of CZ from the selachyl alcohol hexosomes led to a significant enhancement (p <0.05) in oral bioavailability (F% = 17%) compared to the control CZ suspension (9%). Analysis of selachyl alcohol hexosomes using small-angle x-ray scattering indicated that neither the presence of CZ (7 mg/g) nor simulated intestinal fluid altered the H 2 nanostructure. Selachyl alcohol is not susceptible to digestion. Prolonged absorption from the selachyl alcohol-based H 2 systems was attributed to the non-digestible nature of the lipid, similar to non-digestible phytantriol cubic (V 2) systems previously reported. Furthermore, the likely presence of non-sink conditions in the gastric compartment provides a drug reservoir requiring gastric emptying to stimulate drug release from the formulation. This study highlights the potential use of non-digestible liquid crystalline systems generally and nanostructured liquid crystalline particles in particular as novel sustained oral drug delivery systems.
KW - Drug delivery
KW - Hexagonal phase
KW - Liquid crystal
KW - Nanostructured particles
KW - Selachyl alcohol
KW - Sustained release
UR - https://www.scopus.com/pages/publications/84862986866
U2 - 10.1007/s13346-011-0045-z
DO - 10.1007/s13346-011-0045-z
M3 - Article
AN - SCOPUS:84862986866
SN - 2190-393X
VL - 1
SP - 429
EP - 438
JO - Drug Delivery and Translational Research
JF - Drug Delivery and Translational Research
IS - 6
ER -