Peroral absorption of octreotide in pigs formulated in delivery systems on the basis of superporous hydrogel polymers.
OBJECTIVE
The aim of this study was to investigate the enhancement of peroral octreotide absorption using delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) polymers.


METHODS
Six female pigs (BW of 23.5 kg) were used in this study. SPH-based delivery systems were made of two components: 1) a conveyor system made of SPH and SPHC; 2) a core that contained octreotide. The core was inserted into the conveyor system (core inside, c.i.) or attached to the surface of the conveyor system (core outside, c.o.). Four different peroral formulations were investigated: c.i., c.o., core outside including trimethyl chitosan chloride (c.o.t.), and octreotide only in the absence of any polymer (o.o.). All formulations were placed in enteric-coated gelatin capsules (size 000) and administered perorally. Intravenous administration was used to determine bioavailability (F) values. Blood samples taken from the cannulated jugular vein were analyzed by radioimmunoassay.


RESULTS
Peroral administration of 15 mg o.o. resulted in low F values of 1.0 +/- 0.6% (mean +/- SEM) whereas c.i. and c.o. administrations resulted in remarkably higher F values of 12.7 +/- 3.6% and 8.7 +/- 2.4%, respectively. By the addition of trimethyl chitosan chloride as an extra absorption enhancer to c.o.t., the highest bioavailability (16.1 +/- 3.3%) was achieved.


CONCLUSIONS
These novel delivery systems based on SPH and SPHC polymers are able to increase the peroral bioavailability of octreotide by mechanical fixation and increasing the retention of the dosage form at the absorption site.
Dorkoosh
Farid A
FA
Department of Pharmaceutical Technology, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
Verhoef
J Coos
JC
Verheijden
Jos H M
JH
Rafiee-Tehrani
Morteza
M
Borchard
Gerrit
G
Junginger
Hans E
HE
D000042:Absorption / Q000502:physiology; D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D020100:Hydrogels / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015282:Octreotide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016062:Porosity; D013552:Swine
D020100:Hydrogels; D011108:Polymers; D015282:Octreotide