Enhanced ileal absorption of a hydrophilic macromolecule, pentosan polysulfate sodium (PPS).
An in situ gelling, bioadhesive liquid formulation was developed to enhance the bioavailbility (BA) of a polysaccharide, pentosan polysulfate sodium (PPS). The formulation was tested to determine its bioavailability enhancement in a non-flush/non-ligated rat ileal model. A potent synergistic effect was found with a gelling agent Cremophor and a permeation enhancer sodium salicylate. The absolute bioavailabilities were 1.9%, 4.6%, 6.3% and 46.4%, respectively, for the PPS solution in saline, sodium salicylate/PPS, Cremophor/PPS and Cremophor/sodium salicylate/PPS. Therefore, we successfully demonstrated the approach of utilizing an in situ gelling/bioadhesive liquid carrier to enhancing the bioavailability of a hydrophilic macromolecule at the distal small intestine.
Dong
Liang
L
ALZA Corporation, 1010 Joaquin Road, P.O. Box 7210, Mountain View, CA 94039-7210, USA. ldong2@alzus.jnj.com
Yum
Alicia
A
Nguyen
Joe
J
Wong
Pat
P
D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D005260:Female; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption; D008297:Male; D009077:Mucins / Q000502:physiology; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012980:Sodium Salicylate / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000493:pharmacokinetics*; D014783:Viscosity
D009077:Mucins; D013501:Surface-Active Agents; D010426:Pentosan Sulfuric Polyester; C000515:cremophor EL; D005990:Glycerol; D012980:Sodium Salicylate