title: Formulation of Granules for Site-Specific Delivery of an Antimicrobial Essential Oil to the Animal Intestinal Tract.
abstract: Owing to proliferation of antibiotic-resistant bacteria, the use of antibiotics for livestock growth promotion is banned in many countries and alternatives to in-feed antibiotics are needed. Cinnamon essential oil exhibits strong in vitro antibacterial activity; however, direct addition of essential oils to animal feed has limited practicality due to their high volatility, odor, fast decomposition, and poor availability in the lower intestines. To solve these problems, we formulated trans-cinnamaldehyde (CIN) with an adsorbent powder and fatty acid via a melt-solidification technique. Core granules of an optimized composition contained up to 48% wt/wt CIN. The granules were then coated with an enteric polymer to impart site-specific release of CIN. CIN was mostly retained in simulated gastric fluid and released rapidly (>80% under 2 h) in simulated intestinal fluids. Rapid CIN autoxidation into cinnamic acid was inhibited by adding 1% vol/vol eugenol, which maintained CIN stability for at least 1 y. The granule formulation increased the antimicrobial activity of CIN against Escherichia coli K88 slightly with a minimum bactericidal concentration of 450 μg/mL for CIN in lauric acid-based granules compared with 550-600 μg/mL for palmitic acid-based granules and free CIN, respectively. These results encourage the potential use of encapsulated CIN for control of animal enteric pathogens by oral in-feed administration.
authors.affiliation: Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada N1G 5C9; Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2.
authors.forename: Yin-Hing
authors.initials: YH
authors.lastname: Ma
authors.affiliation: Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada N1G 5C9.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Guelph Food Research Centre, Agriculture and Agri-Food Canada, Guelph, Ontario, Canada N1G 5C9.
authors.forename: Joshua
authors.initials: J
authors.lastname: Gong
authors.affiliation: Advanced Pharmaceutics and Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2. Electronic address: xywu@phm.utoronto.ca.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry*; D001826:Body Fluids / Q000378:metabolism / Q000382:microbiology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D004926:Escherichia coli / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000382:microbiology; D009822:Oils, Volatile / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000890:Anti-Infective Agents; D005227:Fatty Acids; D009822:Oils, Volatile; D011108:Polymers; D011208:Powders; D000171:Acrolein; C012843:cinnamaldehyde
keywords: anti-infectives; antioxidants; coating; formulation; oral drug delivery; site-specific delivery; stability