Oil-cyclodextrin based beads for oral delivery of poorly-soluble drugs.

ABSTRACT

The main interest of cyclodextrins results from their ability to form inclusion complexes with hydrophobic molecules. This property is employed in pharmaceutical industry to facilitate the formulation of poorly-soluble and/or fragile drugs. Cyclodextrins are also used to form or stabilise dispersed systems. An original multiparticulate system named "beads" is obtained thanks to the interactions occurring between the molecules of α cyclodextrin and the triglycerides of vegetable oils. Beads are prepared by a simple process involving the external shaking of a mixture of an aqueous solution of α cyclodextrin with soybean oil. This is done without any organic solvent or surface-active agent. Once freezedried, beads have a diameter of 1.6 mm and a high lipid content. They consist in a partially crystalline matrix of cyclodextrin surrounding microdomains of oil. The coating of beads with a layer of α cyclodextrin improves their resistance in gastro- intestinal fluids and prolongs the release of drugs. Beads can also be manufactured from mineral oils with α cyclodextrin and from silicone oils with γ cyclodextrin. Poorly-soluble drugs which do not form inclusion complexes with α cyclodextrin are encapsulated in beads with high efficiency and drug loading. In rats, the oral bioavailability of isotretinoin is twofold enhanced with uncoated beads as compared to the lipid content of a soft capsule. The relative oral bioavailability of indomethacin is improved with both coated and uncoated beads versus a commercial hard capsule. Beads demonstrate an important potential for the encapsulation of poorly-soluble and/or fragile compounds and their delivery by oral route.