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Title: Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell culture and in vivo on rabbit nasal mucosa
Authors: Ugwoke, M I ×
Agu, R U
Jorissen, Mark
Augustijns, Patrick
Sciot, Raphael
Verbeke, Norbert
Kinget, Renaat #
Issue Date: Apr-2000
Series Title: European Journal of Pharmaceutical Sciences vol:9 issue:4 pages:387-96
Abstract: OBJECTIVE: The objective of this study was to investigate the nasal toxicity of a mucoadhesive Carbopol 971P formulation of apomorphine. MATERIALS AND METHODS: The effects of different concentrations of Carbopol 971P and apomorphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. Different groups of the rabbits received twice daily, air puffs, glucose, glucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (glucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). RESULTS: Both Carbopol 971P and apomorphine showed both concentration- and time-dependent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1.0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibition; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomorphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with duration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. CONCLUSIONS: Due to the severe inflammation caused by Carbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This is in spite of the reversible effects of Carbopol 971P (0.1 and 0. 25% w/v) and apomorphine (0.1 and 0.5% w/v) on CBF.
URI: 
ISSN: 0928-0987
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Oto-rhino-laryngology
Drug Delivery and Disposition
Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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