Effect of nano graphene oxide (nGO) incorporation on the lipophilicity of hydrophobic drugs

Abstract

Lipophilicity is a measure of partitioning of an active pharmaceutical ingredient (API) in a lipophilic phase and has been shown to affect gastrointestinal absorption. If a hydrophobic API is completely water insoluble; it does not dissolve in the aqueous phase and is not available for absorption in the gastrointestinal (GI) lipid layer. Therefore, an optimum lipophilicity is important for enhanced bioavailability. It is typically measured as logP or log (Octanol-Water partition coefficient). While water soluble drugs tend to have negative values, high logP can be a problem with insoluble drugs. There are no strict guidelines on logP for hydrophobic drugs, but typically a logP between 0 and 2 is desirable. In this paper, we represent the lowering of logP of hydrophobic API via the successful incorporation of 0.5–2.0% of nanographene oxide (nGO). Four hydrophobic drugs namely Griseofulvin (GF), Dexamethasone (DXM), Apixaban (APX) and Megestrol Acetate (MA) were tested at physiological/intestine pH of 6.0, 7.0, and 8.0 to estimate partitioning behavior. The increased nGO incorporation led to the substantial decrease in logP of all the nGO formulated drugs at all pH as compared to pure drugs. In the cases of GF, APX and MA, the logP decreased from over 2.0 to somewhere between 1.0 and 2.0, and for DXM these decreased to negative values thus making it behave like a water soluble API. The maximum decrease in logP for DXM, GF, APX and MA were 157, 54, 61 and 64% respectively. In summary, the nGO incorporation is an effective means to lower logP and may significantly lead to improved biological absorption and therapeutic efficacy. We believe that current study is very promising for improving efficacy and potentially lowering drug dosage.