Characterization of the Partition Rate of 2-Naphthol (NAP) and Ritonavir (RTV) Across the Water-Octanol Interface and the Influence of Common Pharmaceutical Excipients.

The partition rate of 2 model compounds, 2-naphthol (NAP) and ritonavir (RTV), across the water-octanol (W/O) interface was determined from aqueous solutions with and without the presence of a variety of common pharmaceutical excipients. The NAP molecule was present as either a unionized species in the phosphate buffer solution or as an anion in 0.01 M NaOH solution while RTV was present as dications in 0.1 M HCl. Excipients examined include different type of polymers (e.g., PVP-VA, HPMC, HPMCAS, PVP, PEG 8000), small molecules (e.g., glucose, lactose, maltoheptaose), and surfactants (e.g., Tween 80 and SDS). A noticeable to significant reduction of the partition rate of both NAP and RTV across the W/O interface was observed with aqueous media containing 0.01-0.1 μg/mL polymers including PVP-VA, HPMC, and HPMCAS. Reduction of NAP and RTV partition rate associated with such extremely low concentration of polymers in the aqueous media affirms the presence of a surface excess of adsorbed excipients at the W/O interface. Pi values of NAP and RTV across the W/O interface are found to be sensitive to (1) the molecule surface area, molecular weight and the degree of the polymerization of these pharmaceutical excipients, and (2) the ionization state of the model compound.