In vivo evaluation of lipid-based formulations for oral delivery of apomorphine and its diester prodrugs

[Display omitted] In the present study, the differences in oral absorption of apomorphine and its diester prodrugs and the effect of lipid-based formulations on the absorption of apomorphine or its prodrugs were investigated. Apomorphine, dilauroyl apomorphine (DLA) and dipalmitoyl apomorphine (DPA) were orally administered (0.24mmol/kg) to rats as: DLA-o/w emulsion, DPA-o/w emulsion, apomorphine-o/w emulsion, apomorphine aqueous suspension, DLA-Maisine, DLA-soybean oil, DLA-self-emulsifying drug delivery systems (SEDDS), and DLA-w/o emulsion. The o/w and w/o emulsion consisted of Maisine 35-1 emulsified with water in 1:3 and 4:1 ratio, respectively. Tmax of diesters was significantly increased (p≤0.05) compared to apomorphine in o/w emulsion, suggesting that esterification yielded prolonged drug absorption. Cmax, AUC and the relative bioavailability of apomorphine after DLA-SEDDS administration was higher (p≤0.05) than after DLA-w/o administration, indicating that triglycerides and surfactants improved the oral absorption of DLA. Similarly, Cmax and AUC after dosing apomorphine-o/w were significantly higher (p≤0.05) than that of aqueous suspension. This suggested that lipids and lipolysis products possibly aided apomorphine micellar solubilization in intestinal fluids. A combination of prodrug strategy and lipid-based formulations facilitated a higher and prolonged absorption of apomorphine from its diester prodrugs.