Evaluation of salmon calcitonin (sCT) enteric-coated capsule for enhanced absorption and GI tolerability in rats.
BACKGROUND
Considering the chronic and repeated nature of salmon calcitonin (sCT) therapy, the oral route is a preferred route of administration. But, the oral bioavailability of sCT is very low due to enzymatic degradation and poor permeation across intestinal epithelial cells. It was the aim of this study to investigate the pharmacodynamic (PD), pharmacokinetic (PK), and mucosal injury characteristic of sCT oral delivery system.


METHODS
In this study, PD experiments were performed to find a suitable releasing region of sCT, an effect absorption enhancer, and an optimal mass ratio of sCT/enhancer. In addition, the PK experiments were designed to validate the absorption enhancement of this oral delivery system. Histopathological evaluations on the intestinal mucosa were carried out to assess any potential toxicity of the absorption enhancer.


RESULTS
Through the PD research, we determined that oral sCT enteric-coated capsules containing sCT and citric acid (CA) with a ratio of 1:20 may be an adaptable delivery. PK study further proved that the oral absorption of sCT was enhanced from this delivery system. Finally, no damage on intestinal mucosa was observed when rats received the delivery system containing CA for up to 7 days.


CONCLUSIONS
These results suggested that enteric-coated capsules with a certain amount of CA might give enhanced oral delivery of peptide drugs like sCT.
Wu
Lei
L
Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
Zhang
Ge
G
Lu
Qin
Q
Sun
Qian
Q
Wang
Mulan
M
Li
Na
N
Gao
Zidong
Z
Sun
Ya
Y
Li
Tingting
T
Han
Deen
D
Yu
Xue
X
Wang
Lei
L
Sun
Wei
W
Zhao
Di
D
Wu
Yaning
Y
Lu
Yang
Y
Chen
Xijing
X
D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002116:Calcitonin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D006207:Half-Life; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D050071:Bone Density Conservation Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D019343:Citric Acid; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium