Assessment of the in-vivo drug release from pellets film-coated with a dispersion of high amylose starch and ethylcellulose for potential colon delivery.
OBJECTIVE
The aim of this study was to test the ability of a colon targeting system comprising pellets film-coated with a dispersion of high amylose starch (Hylon VII) and ethylcellulose (Surelease) (1 : 2 w/w) to deliver a model drug (5-aminosalicylic acid; 5-ASA) in vivo into the colon of rabbits. An uncoated pellet formulation was used as a control.


METHODS
Six New Zealand female rabbits, approximately 2 kg, were randomly divided into two groups. Pellet formulations containing 50 mg/kg of 5-ASA were filled into hard gelatin capsules size 4, and were administered orally using a cannula. The rabbits were fasted for 12 h before, and throughout, the study but had free access to water. Blood samples were collected, through a catheter inserted into the marginal vein of the ear, at pre-determined times and the plasma analysed by a validated HPLC method with fluorescence detection.


RESULTS
Analysis of the 5-ASA plasma levels following administration of the uncoated pellets showed a C(max) of 2.38 +/- 0.49 microg/ml at 2 h post administration confirming that this system released the drug at an unspecific site, most likely in the rabbits' stomach and proximal small intestine. On the other hand, the coated formulation showed a delayed drug absorption (C(max) 0.22 +/- 0.19 microg/ml and t(max) of 8 h), suggesting that the coating is able to prevent drug release in the stomach and small intestine, but allowing drug release in the colon. The coated pellets were retrieved from the rabbits' faeces after the 24-h study. They had a drug content of < 40%, suggesting that the film-coating had been digested by the bacterial amylases of the colon and the drug was released specifically in the colon of the rabbits.


CONCLUSIONS
Results from this study showed that the proposed drug delivery system has the potential to deliver drugs specifically into the colon.
Freire
Cristina
C
Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde Azinhaga de Santa Comba, Coimbra, Portugal. anacfreire80@hotmail.com
Podczeck
Fridrun
F
Ferreira
Dinora
D
Veiga
Francisco
F
Sousa
João
J
Pena
Angelina
A
D000688:Amylose / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003106:Colon / Q000378:metabolism*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D007408:Intestinal Absorption; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D019804:Mesalamine; C013517:ethyl cellulose; D002482:Cellulose; D000688:Amylose