An in situ crosslinked compression coat comprised of pectin and calcium chloride for colon-specific delivery of indomethacin.
The use of pectin for colon-specific drug delivery has been extensively investigated; however, when used alone, pectin is often compromised due to its high solubility. This study explored the feasibility of using an in situ compression-coated crosslinking system, composed of pectin and calcium chloride, for colon-specific drug delivery. A pectin/calcium chloride (P/Ca) coating was compressed onto a core tablet. The colon specificity of the compression-coated tablet was verified by dissolution, pharmacokinetics and scintigraphy with (99m)Tc labeling. The in situ pectin and calcium chloride gel slowed the release of indomethacin. The lag time varied between 3 h and 7 h depending on the amount of calcium chloride and the coating weight. Pectinase triggered the release of indomethacin from the compression-coated tablet, which was then accelerated by the calcium chloride in the coating layer. The compression-coated tablet had a prolonged tmax and apparent t1/2, as well as a decreased Cmax and AUC0-t, compared with the core tablet counterpart. Evaluation with γ-scintigraphy verified colon-specific delivery of the compression-coated tablet. In conclusion, the P/Ca in situ crosslinking system worked well for colon-specific drug delivery.
Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, School of Pharmacy, Fudan University , Shanghai , China and.
Xiuli
X
Wei
Yi
Y
Lu
Jianping
J
Qi
Baojian
B
Wu
Jian
J
Chen
Huinan
H
Xu
Wei
W
Wu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002122:Calcium Chloride / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004285:Dogs; D065546:Drug Liberation; D005766:Gastrointestinal Contents / Q000737:chemistry / Q000201:enzymology; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D010368:Pectins / Q000737:chemistry*; D011877:Radionuclide Imaging; D051381:Rats; D013608:Tablets, Enteric-Coated
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003432:Cross-Linking Reagents; D013608:Tablets, Enteric-Coated; D010368:Pectins; D002122:Calcium Chloride; D007213:Indomethacin
Calcium chloride; colon; compression coated; in situ crosslinking; indomethacin; pectin; tablet