Shirley A Aguirre1,2, Hovhannes J Gukasyan3, Husam S Younis4, Wenhu Huang5. 1. Pfizer Inc., Drug Safety Research and Development, La Jolla Laboratories, 10646 Science Center Drive, San Diego, CA, 92121, USA. shirleyaaguirre@gmail.com. 2. Virchow Toxpath LLC, PO Box 12830, Prescott, AZ, 86304, USA. shirleyaaguirre@gmail.com. 3. Allergan, 2525 Dupont Dr, Irvine, CA, 92612, USA. 4. NGM Biopharmaceuticals, Inc., 630 Gateway Blvd, South San Francisco, CA, 94080, USA. 5. Pfizer Inc., Drug Safety Research and Development, La Jolla Laboratories, 10646 Science Center Drive, San Diego, CA, 92121, USA.
Abstract
PURPOSE: Evaluate 21 formulation vehicles administered to rabbits after intravitreal injection for tolerability and safety. METHODS: Forty-two Dutch Belted rabbits were anesthetized, and the eyes received a single intravitreal injection of the excipient formulation. Clinical signs and ocular irritation responses were recorded twice daily for 7 days and microscopic evaluation of the eyes, optic nerve, and eyelids was completed at 1-week post treatment. RESULTS: Saline (≥ 300 mOsm and ≤ 592 mOsm at pH 7.0 or 300 mOsm at pH 8.0) and 10 formulation excipients; (10% w/v PEG 3350 at pH 7.4, 1% polysorbate 21 at pH 7.4, PVA at pH 7.0, 0.2% polysorbate 80 at pH 7.2, 0.2% Pluronic F108® at pH 7.3, 2%, 100 mM sodium sulfate at pH 3.2, 2 mM sodium glycocholate at pH 7.4, and 275 mM D-mannitol pH 7.0 in sterile water, and 100 mM sodium phosphate in combination with 0.9% NaCl 300 mOsm and 0.01% or 0.05% polysorbate 80 at pH 7.4) considered as formulation vehicles for intravitreal injectables, were well-tolerated in rabbits. Clinical signs were transient and microscopic changes were not observed. CONCLUSIONS: Of the 21 formulation vehicles evaluated, 10 formulation vehicles were well-tolerated in rabbits and feasible candidates for future investigations.
PURPOSE: Evaluate 21 formulation vehicles administered to rabbits after intravitreal injection for tolerability and safety. METHODS: Forty-two Dutch Belted rabbits were anesthetized, and the eyes received a single intravitreal injection of the excipient formulation. Clinical signs and ocular irritation responses were recorded twice daily for 7 days and microscopic evaluation of the eyes, optic nerve, and eyelids was completed at 1-week post treatment. RESULTS: Saline (≥ 300 mOsm and ≤ 592 mOsm at pH 7.0 or 300 mOsm at pH 8.0) and 10 formulation excipients; (10% w/v PEG 3350 at pH 7.4, 1% polysorbate 21 at pH 7.4, PVA at pH 7.0, 0.2% polysorbate 80 at pH 7.2, 0.2% Pluronic F108® at pH 7.3, 2%, 100 mM sodium sulfate at pH 3.2, 2 mM sodium glycocholate at pH 7.4, and 275 mM D-mannitol pH 7.0 in sterile water, and 100 mM sodium phosphate in combination with 0.9% NaCl 300 mOsm and 0.01% or 0.05% polysorbate 80 at pH 7.4) considered as formulation vehicles for intravitreal injectables, were well-tolerated in rabbits. Clinical signs were transient and microscopic changes were not observed. CONCLUSIONS: Of the 21 formulation vehicles evaluated, 10 formulation vehicles were well-tolerated in rabbits and feasible candidates for future investigations.
Authors: Rob Webster; Eric Didier; Philip Harris; Ned Siegel; Jeanne Stadler; Lorraine Tilbury; Dennis Smith Journal: Drug Metab Dispos Date: 2006-10-04 Impact factor: 3.922
Authors: Suma Gopinathan; Emily O'Neill; Lawrence A Rodriguez; Rose Champ; Megan Phillips; Amr Nouraldeen; Mary Wendt; Alan G E Wilson; Jeffrey A Kramer Journal: J Pharmacol Toxicol Methods Date: 2013-03-14 Impact factor: 1.950