Are in vivo gastric bioadhesive forces accurately reflected by in vitro experiments?
Bioadhesive polymers have been used in oral drug delivery to prolong the contact of dosage forms with the site of drug absorption. Previous investigators have coated oral dosage forms in polymers that demonstrated bioadhesive properties during in vitro screens in efforts to prolong the gastric residence of drugs absorbed only in the stomach and proximal duodenum without clinical success. To further investigate the bioadhesive properties of the gastric environment, an in vivo quantitative bioadhesive fracture strength test was developed. Bioadhesive and non-bioadhesive bioerodible polymers with potential for use in oral drug delivery were tested for bioadhesive fracture strength both in vivo and in vitro. Surprisingly, no statistically significant difference was found between the bioadhesive fracture strength of fast eroding polyanhydride and slowly eroding hydrophobic polymers in vivo. When the same polymers were tested in vitro, the expected difference was observed. The lack of IVIVC (in vitro/in vivo correlation) among bioadhesive fracture strengths reflects the clinical finding that polymers that produced strong bioadhesive forces in vitro may not achieve prolonged gastric retention in vivo due to differences between the in vitro screening conditions and the in vivo bioadhesive environment.
Laulicht
Bryan
B
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, RI 02912, USA.
Cheifetz
Peter
P
Tripathi
Anubhav
A
Mathiowitz
Edith
E
D000268:Adhesiveness; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry; D005753:Gastric Mucosa / Q000737:chemistry*; D008422:Materials Testing / Q000379:methods*; D023421:Models, Animal; D049388:Polyanhydrides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D003692:Delayed-Action Preparations; D049388:Polyanhydrides