In vitro and in vivo evaluation of a novel capsule for colon-specific drug delivery.
The aim of this study was to estimate colon-specific drug delivery of a novel capsule (CS capsule). Theophylline was used as model drug and little was released from the CS capsules in the release medium mimicking physiological environment of stomach to small intestine. However, 66.7 +/- 8.8% theophylline was released from the capsules in the phosphate buffer (pH 6.8) mimicking the physiological environment of colon in the next 4 h, while the addition of galactomannanase (39.3 U/L) accelerated the disintegration of the CS capsule and enhanced the release rate to 92.6 +/- 6.0%. Rats in vivo pharmacokinetics demonstrated that the relative bioavailability of theophylline after intragastric administration of CS capsules was 76.72% with delayed T(max) of 8 h comparing to that of theophylline solution with T(max) of 1.5 h. Radiolabeled with technetium-99m, the CS capsule could keep intact from stomach to small intestine while disintegration of the CS capsule was observed in the proximal colon or the joint between the distal small intestine and right colon. A great quantity of radiolabeled marker was released as well as distributed in the whole colon at 10 h after administration. As a whole, the CS capsule prepared could provide an alternative carrier for the colon-specific drug delivery.
Han
Min
M
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, China.
Fang
Qiu-Li
QL
Zhan
Hong-Wei
HW
Luo
Tao
T
Liang
Wen-Quan
WQ
Gao
Jian-Qing
JQ
D000328:Adult; D000818:Animals; D002214:Capsules / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008297:Male; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics; D055815:Young Adult
D002214:Capsules; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D013806:Theophylline