title: Dry powder dosing in liquid vehicles: ocular tolerance and scintigraphic evaluation of a perfluorocarbon suspension.
abstract: The ocular tolerance and precorneal disposition of 99mTc-labelled sterile carbon-perfluorodecalin (PFD) and carbon-aqueous suspensions were examined in a cohort of healthy volunteers. Formulations were prepared in PFD or saline using charcoal particles, radiolabelled with [99mTc]diethylenetriaminepentaacetic acid (DTPA) under GMP conditions. Colloidal silicon dioxide was used as a suspending agent. Ocular tolerance was examined following the instillation of each formulation to the eyes of 12 volunteers. The precorneal distribution of both formulations in man was monitored using gamma scintigraphy. Dynamic and static data acquisitions were taken over a period of 150 min after dosing. Carbon particulates suspended in PFD did not show any irritation to the eye. Administration of PFD formulation in man produced a significant increase in ocular retention over a saline formulation (mean residence time (MRT)=157+/-42 and 0.29+/-0.08 min, respectively, P=0.0001). Distribution of the carbon in man followed the same pattern as in a previous reported study in animals. The carbon deposited uniformly along the lid margin in the case of the PFD vehicle, whereas it agglomerated following dosing in the saline vehicle and was ejected from the eye. The novel non-aqueous vehicle system is able to significantly improve the ocular retention of charcoal particles in man and provides a unique distribution of the particles in the eye, which suggests a potential for the PFD system for the treatment of periocular diseases.
authors.affiliation: Department of Pharmaceutical Sciences, Royal College, University of Strathclyde, Glasgow, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: C G
authors.initials: CG
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Meadows
authors.forename: O
authors.initials: O
authors.lastname: Olejnik
authors.forename: M
authors.initials: M
authors.lastname: Frier
authors.forename: N
authors.initials: N
authors.lastname: Washington
authors.forename: R
authors.initials: R
authors.lastname: Musson
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002606:Charcoal; D005123:Eye / Q000187:drug effects; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000009:adverse effects* / Q000032:analysis; D006801:Humans; D007509:Irritants / Q000009:adverse effects; D008297:Male; D011208:Powders; D019275:Radiopharmaceuticals; D013535:Suspensions; D016284:Technetium Tc 99m Pentetate
chemical_list: D005466:Fluorocarbons; D007509:Irritants; D011208:Powders; D019275:Radiopharmaceuticals; D013535:Suspensions; D002606:Charcoal; D016284:Technetium Tc 99m Pentetate