title: Oral liquid in situ gelling methylcellulose/alginate formulations for sustained drug delivery to dysphagic patients.
abstract: BACKGROUND
  Elderly patients with swallowing dysfunction may benefit from the oral administration of liquid dosage forms with in situ gelling properties.
  
  
  OBJECTIVE
  We have designed in situ gelling liquid dosage formulations composed of mixtures of methylcellulose, which has thermally reversible gelation properties and sodium alginate, the gelation of which is ion-responsive, with suitable rheological characteristics for ease of administration to dysphagic patients and suitable integrity in the stomach to achieve a sustained release of drug.
  
  
  METHODS
  The rheological and gelation characteristics of solutions containing methylcellulose (2.0%) and sodium alginate (0.25-1.0%) were assessed for their suitability for administration to dysphagic patients. The gel strength and in vitro and in vivo release characteristics of gels formed by selected formulations were compared using paracetamol as a model drug.
  
  
  RESULTS
  Mixtures of 2.0% methylcellulose and 0.5% alginate containing 20% d-sorbitol were of suitable viscosity for ease of swallowing by dysphagic patients and formed gels at temperatures between ambient and body temperature allowing administration in liquid form and in situ gelation in the stomach. In vitro release of paracetamol from 2.0% methylcellulose/0.5% alginate gels was diffusion-controlled at pH 1.2 and 6.8. Measurement of plasma levels of paracetamol after oral administration to rats of a 2.0% methylcellulose/0.5% alginate formulation showed improved sustained release compared to that from 2.0% methylcellulose and 0.5% alginate solutions and from an aqueous solution of paracetamol.
  
  
  CONCLUSIONS
  Solutions of mixtures of methylcellulose and alginate in appropriate proportions are of suitable consistency for administration to dysphagic patients and form gels in situ with sustained release characteristics.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimoyama
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Michiya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Shozo
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Antony
authors.initials: A
authors.lastname: D'Emanuele
authors.forename: David
authors.initials: D
authors.lastname: Attwood
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003680:Deglutition Disorders / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004058:Diffusion; D004304:Dosage Forms; D016503:Drug Delivery Systems / Q000379:methods*; D005753:Gastric Mucosa / Q000378:metabolism; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry*; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000737:chemistry*; D010368:Pectins / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D014783:Viscosity
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D005782:Gels; D006603:Hexuronic Acids; D012996:Solutions; D010368:Pectins; D020723:Glucuronic Acid; D008747:Methylcellulose