Neutron activation based gamma scintigraphic evaluation of enteric-coated capsules for local treatment in colon.
The fate of two colon-specific formulations developed in our previous study was investigated using a gamma scintigraphic imaging method. The formulations contained paracetamol and samarium oxide (Sm2O3) and either microcrystalline cellulose (MCC) or hypromellose (HPMC K4M) as diluent and were coated with Eudragit S polymer. The gamma scintigraphic evaluation proved that the products remained intact in the stomach and the upper gastrointestinal tract. The gastric residence time was less that 1h. Three to four hours after administration the formulations had reached the ileo-caecal junction, i.e. the small intestine transit time was approximately 3h. The capsules disintegrated in the ileo-caecal junction or in the ascending colon. The capsules containing MCC released the marker momentarily, the capsules containing HPMC K4M gradually spreading it to the whole colon. The gamma images also verified that the HPMC gel disintegrates completely in 12-14 h. While comparing the results to those previously obtained from the bioavailability studies it could be concluded that it is possible to develop colon specific drug products that begin releasing the drug in the ileo-caecal junction or at the beginning of the ascending colon and spread the drug dose to a larger surface area by using enteric coats and hydrophilic polymers.
Marvola
Tuuli
T
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 University of Helsinki, Finland. tuuli.marvola@helsinki.fi
Marvola
Janne
J
Kanerva
Hanna
H
Ahonen
Aapo
A
Lindevall
Kai
K
Marvola
Martti
M
D000082:Acetaminophen / Q000008:administration & dosage / Q000493:pharmacokinetics; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000493:pharmacokinetics; D001682:Biological Availability; D002482:Cellulose; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000000981:diagnostic imaging / Q000187:drug effects*; D016503:Drug Delivery Systems; D005079:Excipients; D005720:Gamma Rays; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives; D009501:Neutron Activation Analysis; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids; D011877:Radionuclide Imaging; D012493:Samarium / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000737:chemistry* / Q000493:pharmacokinetics
D018712:Analgesics, Non-Narcotic; D005079:Excipients; D010087:Oxides; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; C038300:methylmethacrylate-methacrylic acid copolymer; D000082:Acetaminophen; D065347:Hypromellose Derivatives; D012493:Samarium; D002482:Cellulose; D008747:Methylcellulose; C120592:samarium oxide; C109691:microcrystalline cellulose