Enhanced Oral Bioavailability of a Poorly Water Soluble Drug PNU‐91325 by Supersaturatable Formulations

Abstract

Supersaturatable cosolvent (S‐cosolvent) and supersaturatable self‐emulsifying drug delivery systems (S‐SEDDS) are designed to incorporate water soluble cellulosic polymers such as hydroxypropyl methylcellulose (HPMC), which may inhibit or retard drug precipitation in vivo. A poorly soluble drug, PNU‐91325, was used as a model drug in this study to illustrate this formulation approach. The comparative in vitro studies indicated that the presence of a small amount HPMC in the formulation was critical to achieve a stabilized supersaturated state of PNU‐91325 upon mixing with water. An in vivo study was conducted in dogs for assessment of the oral bioavailability of four formulations of PNU‐91325. A five‐fold higher bioavailability (∼ 60%) was observed from a S‐cosolvent formulation containing propylene glycol (PG) + 20 mg/g HPMC as compared to that (∼ 12%) of a neat polyethylene glycol (PEG) 400 formulation. The low bioavailability of the PEG 400 formulation is attributed to the uncontrolled precipitation o...