Evaluation of the mucosal irritation potency of co-spray dried Amioca®/poly (acrylic acid) and Amioca®/Carbopol® 974P mixtures

The purpose of this study was to evaluate the biocompatibility of different Amioca((R))/poly(acrylic acid) and Amioca((R))/ Carbopol((R)) 974P co-spray dried mixtures with an alternative mucosal irritation test using slugs. The irritation potential of the mixtures was measured by the amount Of MUCUS produced during a repeated 30-min contact period. Additionally, membrane damage was assessed by measuring the protein and enzyme release from the body wall of slugs after treatment. All the Amioca((R))/poly(acrylic acid) co-spray dried mixtures (50:50 and 25:75 ratios) induced slight irritation of the mucosal tissue as was demonstrated by the significantly increased mucus production however no increased protein and enzyme release was detected. Co-spray dried Amioca((R))/Carbopol 974P mixtures containing 40% and more Carbopol((R)) 974P demonstrated a significantly higher mucus production and release of cytosolic LDH, indicating membrane damage. The total MUCUS production of the slugs treated with the co-spray dried mixtures containing up to 20% Carbopol((R)) 974P was significantly higher compared to the blank slugs. However, these mixtures induced no membrane damage since no additional effect on the protein release and no enzyme release was detected. By co-spray drying up to 20% Carbopol((R)) 974P could he incorporated without showing a distinct sign of irritation. These mixtures can be considered as potentially safe bioadhesive carriers. (C) 2003 Elsevier Science B.V. All rights reserved.