Dry powder dosing in liquid vehicles: ocular tolerance and scintigraphic evaluation of a perfluorocarbon suspension

The ocular tolerance and precorneal disposition of Tc-99m-labelled sterile carbon-perfluorodecalin (PFD) and carbon-aqueous suspensions were examined in a cohort of healthy volunteers. Formulations were prepared in PFD or sal ine using charcoal particles, radiolabelled with [Tc-99m]diethylenetriamine pentaacetic acid (DTPA) under GMP conditions. Colloidal silicon dioxide was used as a suspending agent. Ocular tolerance was examined following the in stillation of each formulation to the eyes of 12 volunteers. The precorneal distribution of both formulations in man was monitored using gamma scintig raphy. Dynamic and static data acquisitions were taken over a period of 150 min after dosing. Carbon particulates suspended in PFD did not show any ir ritation to the eye. Administration of PFD formulation in man produced a si gnificant increase in ocular retention over a saline formulation (mean resi dence time (MRT) = 157 +/- 42 and 0.29 +/- 0.08 min, respectively, P = 0.00 01). Distribution of the carbon in man followed the same pattern as in a pr evious reported study in animals. The carbon deposited uniformly along the lid margin in the case of the PFD vehicle, whereas it agglomerated followin g dosing in the saline vehicle and was ejected from the eye. The novel non- aqueous vehicle system is able to significantly improve the ocular retentio n of charcoal particles in man and provides a unique distribution of the pa rticles in the eye, which suggests a potential for the PFD system for the t reatment of periocular diseases. (C) 1999 Elsevier Science B.V. All rights reserved.