Development of pH- and enzyme-controlled, colon-targeted, pulsed delivery system of a poorly water-soluble drug: preparation and in vitro evaluation.
BACKGROUND
As conventional pH-controlled colon-targeted system used for oral drug delivery often shows a poor performance, a more effective way to preserve poorly water-soluble drug from releasing in upper gastrointestinal tract should be researched.


METHODS
The objective of this study was to develop a novel colon-targeted drug delivery system using guar gum and Eudragit as enzyme- and pH-based materials. Lansoprazole, a poorly water-soluble drug was used as model drug. Under three different conditions, the in vitro drug release behaviors of this newly developed system was evaluated, using β-mannanase, rat cecal content, and human fecal media to simulate the pH and enzyme during intestinal transit to the colon.


RESULTS
The released amount of lansoprazole in simulated small intestine fluid (pH 6.8) after 5 hours was less than 10% from the pH- and enzyme-controlled tablets compared with 80.01±0.3% in rat cecal content medium (pH 7.4).The degradation ability of human fecal slurries on PECCT-PT was independent of human age and gender. β-Mannanase did not have a similar effect on the degradation of polysaccharide as rat cecal enzymes and human fecal enzymes in our study. Scanning electron microscope study indicated that the dissolution mechanism of PECCT-PT should be corrosion.


CONCLUSIONS
The above results indicated this system could be served as a potential carrier to deliver poorly water-soluble drug specifically to the colon.
Lai
Huiming
H
Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, PR China.
Lin
Ke
K
Zhang
Wenbin
W
Zhang
Zhirong
Z
Jie
Liu
L
Wu
Yuna
Y
He
Qin
Q
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000378:metabolism*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D005685:Galactans / Q000737:chemistry; D005772:Gastrointestinal Transit; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D064747:Lansoprazole; D008297:Male; D008351:Mannans / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D053149:Plant Gums / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D012995:Solubility; D055815:Young Adult; D044902:beta-Mannosidase / Q000378:metabolism
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D005079:Excipients; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D011109:Polymethacrylic Acids; D064747:Lansoprazole; C038300:methylmethacrylate-methacrylic acid copolymer; C007894:guar gum; D044902:beta-Mannosidase