title: Enhanced colonic delivery of ciclosporin A self-emulsifying drug delivery system encapsulated in coated minispheres.
abstract: OBJECTIVE
  Investigate the potential of coated minispheres (SmPill®) to enhance localized Ciclosporin A (CsA) delivery to the colon.
  
  
  METHODS
  CsA self-emulsifying drug delivery systems (SEDDS) were encapsulated into SmPill® minispheres. Varying degrees of coating thickness (low, medium and high) were applied using ethylcellulose and pectin (E:P) polymers. In vitro CsA release was evaluated in simulated gastric and intestinal media. Bioavailability of CsA in vivo following oral administration to pigs of SmPill® minispheres was compared to Neoral® po and Sandimmun® iv in a pig model. CsA concentrations in blood and intestinal tissue were determined by HPLC-UV.
  
  
  RESULTS
  In vitro CsA release from coated minispheres decreased with increasing coating thickness. A linear relationship was observed between in vitro CsA release and in vivo bioavailability (r(2) = 0.98). CsA concentrations in the proximal, transverse and distal colon were significantly higher following administration of SmPill®, compared to Neoral® po and Sandimmun® iv (p < 0.05). Analysis of transverse colon tissue subsections also revealed significantly higher CsA concentrations in the mucosa and submucosa using SmPill® minispheres (p < 0.05).
  
  
  CONCLUSIONS
  Modulating E:P coating thickness controls release of CsA from SmPill® minispheres. Coated minispheres limited CsA release in the small intestine and enhanced delivery and uptake in the colon. These findings demonstrate clinical advantages of an oral coated minisphere-enabled CsA formulation in the treatment of inflammatory conditions of the large intestine.
authors.affiliation: a Pharmacodelivery Group, School of Pharmacy, University College Cork , Cork , Ireland and.
authors.forename: Kieran
authors.initials: K
authors.lastname: Keohane
authors.affiliation: b Sigmoid Pharma Ltd., The Invent Centre, Dublin City University , Dublin 9 , Ireland.
authors.forename: Mónica
authors.initials: M
authors.lastname: Rosa
authors.affiliation: b Sigmoid Pharma Ltd., The Invent Centre, Dublin City University , Dublin 9 , Ireland.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Coulter
authors.affiliation: a Pharmacodelivery Group, School of Pharmacy, University College Cork , Cork , Ireland and.
authors.forename: Brendan T
authors.initials: BT
authors.lastname: Griffin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003106:Colon / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005750:Gastric Juice / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007419:Intestinal Secretions / Q000378:metabolism; D008297:Male; D010368:Pectins / Q000737:chemistry; D013552:Swine
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D007166:Immunosuppressive Agents; C013517:ethyl cellulose; D016572:Cyclosporine; D010368:Pectins; D002482:Cellulose
keywords: Bioavailability; coated minispheres; colonic targeting; mucosa; tissue