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Coated minispheres of salmon calcitonin target rat intestinal regions to achieve systemic bioavailability: Comparison between intestinal instillation and oral gavage.
Aguirre, Tanira A S; Aversa, Vincenzo; Rosa, Mónica; Guterres, Sílvia S; Pohlmann, Adriana R; Coulter, Ivan; Brayden, David J.
Afiliación
  • Aguirre TAS; UCD School of Veterinary Science and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland; Sigmoid Pharma, Dublin City University, Invent Centre, Dublin 9, Ireland.
  • Aversa V; Sigmoid Pharma, Dublin City University, Invent Centre, Dublin 9, Ireland.
  • Rosa M; Sigmoid Pharma, Dublin City University, Invent Centre, Dublin 9, Ireland.
  • Guterres SS; Programa de pós Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • Pohlmann AR; Programa de pós Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • Coulter I; Sigmoid Pharma, Dublin City University, Invent Centre, Dublin 9, Ireland.
  • Brayden DJ; UCD School of Veterinary Science and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: david.brayden@ucd.ie.
J Control Release ; 238: 242-252, 2016 09 28.
Article en En | MEDLINE | ID: mdl-27480451
Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45µmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vehículos Farmacéuticos / Calcitonina / Conservadores de la Densidad Ósea / Absorción Intestinal Límite: Animals / Humans / Male Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vehículos Farmacéuticos / Calcitonina / Conservadores de la Densidad Ósea / Absorción Intestinal Límite: Animals / Humans / Male Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Irlanda Pais de publicación: Países Bajos