Novel beads made of alpha-cyclodextrin and oil for topical delivery of a lipophilic drug.

PURPOSE: To investigate the potential of a novel lipid carrier, comprising beads of alpha-cyclodextrin and soybean oil, for topical drug delivery. Adapalene was chosen as a model drug to explore the ability of the beads to encapsulate and release a highly lipophilic compound. MATERIALS AND METHODS: Adapalene-loaded beads were prepared and characterised. Skin tolerance to unloaded beads was tested on human volunteers, while drug release and delivery into stratum corneum, was evaluated in pig skin ex vivo. RESULTS: The preparation and physical characteristics of the beads were not dependent on whether adapalene had been previously dissolved or dispersed in soybean oil. Drug encapsulation efficiency was high (>96%) and drug loading on the order of a therapeutic level could be achieved in freeze-dried beads prepared from an oily dispersion of adapalene. After application to human skin, unloaded beads induced no adverse reaction and were better tolerated than an alcoholic gel. Tape-stripping the stratum corneum from treated pig skin showed that adapalene release and penetration from the beads was comparable to that from gel and cream formulations available on the market. CONCLUSION: These novel beads may offer a well-tolerated and efficient system for the encapsulation and topical delivery of lipophilic drugs.

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.