Alpha-cyclodextrin/oil beads as a new carrier for improving the oral bioavailability of lipophilic drugs.
The purpose of the present work was to investigate the potential of novel lipid-carrier "beads" consisting of minispheres made of alpha-cyclodextrin and soybean oil for the encapsulation and the oral delivery of drugs. Isotretinoin was chosen as a model of poorly-stable and lipophilic molecule. Isotretinoin-loaded beads were prepared, characterised and administrated orally in rats. Isotretinoin previously dissolved in soybean oil had no significant effect upon bead preparation and characteristics. Drug encapsulation efficiency was found to be particularly high (93+/-7%) and no isotretinoin degradation occurred during the preparation process. Freeze-drying advantageously concentrated isotretinoin in beads (3.4+/-0.2 mg/g) and facilitating ease of handling and use for oral administration. Isotretinoin exhibited good stability for at least 4 months when beads were stored protected from light. Finally, pharmacokinetics of isotretinoin in rats demonstrated that the drug was successfully released from beads in the digestive tract and that isotretinoin absolute bioavailability was doubled compared to isotretinoin lipid solution (32% and 15% respectively). In conclusion, these beads constitute a novel and efficient system for encapsulation and oral delivery of lipophilic and fragile drugs.
Trichard
Laury
L
Univ Paris-Sud, CNRS UMR 8612, Physico-chimie-Pharmacotechnie-Biopharmacie, Faculté de Pharmacie, Châtenay-Malabry, France.
Fattal
Elias
E
Besnard
Madeleine
M
Bochot
Amélie
A
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D015474:Isotretinoin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D010316:Particle Size; D010938:Plant Oils / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D013024:Soybean Oil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D047391:alpha-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
D004337:Drug Carriers; D010938:Plant Oils; D012996:Solutions; D047391:alpha-Cyclodextrins; D013024:Soybean Oil; D015474:Isotretinoin