Examination of the impact of a range of Pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquone

Exogenous surfactants are increasingly used to enhance the dispersion properties of lipid‐based formulations of poorly water‐soluble drugs, yet their possible effects on formulation digestion and oral bioavailability in‐vivo are not well documented. In this study, in‐vitro dispersion and digestion experiments were conducted using formulations comprising a blend of long‐chain glycerides, ethanol, a model poorly water‐soluble drug (atovaquone), and a series of surfactants including Cremophor EL and a range of Pluronic surfactants (Pluronics L121, L61, L72, L43 and F68). Inclusion of Cremophor EL, a surfactant with a high hydrophilic‐lipophilic balance (HLB), promoted complete digestion of the formulation and effective dispersion and solubilisation of the lipolytic products and co‐administered drug. Surprisingly, formulations containing the Pluronic (L121) with the lowest HLB (0.5) equally effectively promoted digestion and drug solubilisation and a trend towards decreased digestion and drug solubilisation was observed with Pluronics of increasing HLB values. All formulations effectively prevented drug precipitation, suggesting possible utility in‐vivo, and no correlation was evident between the ability of the formulations to self‐emulsify on dispersion and to promote drug solubilisation on digestion. Subsequent assessment of the oral bioavailability of atovaquone after administration of formulations containing Cremophor EL or Pluronic L121 or a simple solution of atovaquone in long‐chain glycerides confirmed the utility of lipid‐based formulations for enhancing the oral bioavailability of poorly water‐soluble drugs such as atovaquone, but also indicated that in some cases microemulsion preconcentrate formulations may not provide additional bioavail‐ability benefits beyond that achievable using simple lipid solutions.