FORMULATION, IN-VITRO DISSOLUTION, AND OCULAR BIOAVAILABILITY OF HIGH-MELTING AND LOW-MELTING PHENYLEPHRINE OXAZOLIDINES

The in vitro dissolution and the relative ocular bioavailability of hi gh- and low-melting phenylephrine oxazolidines (HMP and LMP) from a no naqueous suspension (silicone fluid) were compared. Stability-indicati ng HPLC assays were developed for evaluation of the prototype formulat ions, in which a normal-phase HPI,C method was necessary for analysis of PO, while a reverse-phase HPLC method was required for analysis of the primary degradation product, phenylephrine (PE), following its sep aration from the formulation using a short silica gel column. PO was f ormulated as an ophthalmic suspension in silicone fluid (20 cs) becaus e of its property of undergoing rapid hydrolysis in aqueous media. An experimental test system for measuring the dissolution characteristics of a water-immiscible multiparticulate suspension was designed to obt ain the dissolution profiles of suspensions of HMP and LMP. The dissol ution rates, which were nearly identical for LMP and HMP, were obtaine d assuming a quasi-infinite reservoir. A reverse-phase HPLC assay with fluorescence detection was used for measuring the concentrations of P E in aqueous humor and corneal samples. Statistical analysis of the bi oavailability data showed that suspensions containing HMP and LMP were equal in extent of absorption following a single topical application to the rabbit eye. The results correlated well with the in vitro disso lution rates of the suspensions of HMP and LMP.