FEASIBILITY OF ZEBRAFISH LARVA MODEL AS A VIABLE SUBSTITUTE TO RAT NON-EVERTED SAC MODEL FOR PERMEATION EVALUATION OF BCS III DRUGS

Abstract

The oral route is the most convenient route of drug administration. Many drugs exhibit poor oral bioavailability. BCS III drugs exhibit high solubility and present a massive challenge due to poor permeability. Different permeation enhancers viz., nonionic Cremophor® RH 40, Tween® 80 and Lutrol® F68, anionic docusate sodium with sodium cholate, and anionic polymer sodium carboxymethyl cellulose were evaluated using rat non-everted sac method and zebrafish larva model. Maximum permeation enhancement was seen with docusate sodium for both drugs. The permeation enhancement ratio for netilmicin sulphate was 4.07±0.657, while for deferoxamine mesylate it was 1.482±0.378. Cremophor® RH 40 enabled augmented flux of netilmicin sulphate, and Tween® 80 showed enhanced permeation of deferoxamine mesylate. An excellent correlation was observed between apparent permeability and flux with drug absorbed per zebrafish larva (µg) (R2 = 0.938) for netilmicin sulphate and for deferoxamine mesylate (R2 = 0.9397). An important outcome of the study is the demonstration of the feasibility of the zebrafish larvae model as a viable substitute to the non-everted sac method, which could also enable screening of potential permeation enhancers for the development of orally bioavailable formulations of BCS III.