title: Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.
abstract: Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms.
authors.affiliation: Department of Chemistry and Centre Pharmaqam, Université du Québec à Montréal, CP 8888, Succ. Centre-Ville, Montréal, Québec H3C 3P8, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Lemieux
authors.affiliation: Corealis Pharma Inc., 200 Boulevard Armand Frappier, Laval, Québec H7V 4A6, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gosselin
authors.affiliation: Department of Chemistry and Centre Pharmaqam, Université du Québec à Montréal, CP 8888, Succ. Centre-Ville, Montréal, Québec H3C 3P8, Canada. Electronic address: mateescu.m-alexandru@uqam.ca.
authors.forename: Mircea Alexandru
authors.initials: MA
authors.lastname: Mateescu
mesh_terms: D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D017097:Electric Impedance; D005665:Furosemide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D005665:Furosemide; D013213:Starch; C034848:carboxymethyl starch
keywords: Carboxymethyl starch microspheres; Cell viability; Drug delivery; Furosemide (PubChem CID 3440); Gastroretentive dosage form; High amylose starch (PubChem CID 53477771); Mucoadhesion; Permeability