Mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide drug buserelin in vivo.
OBJECTIVE
To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin.


METHODS
Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats.


RESULTS
All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as alpha-chymotrypsin.


CONCLUSIONS
The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.
Luessen
H L
HL
Leiden/Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, The Netherlands.
de Leeuw
B J
BJ
Langemeÿer
M W
MW
de Boer
A B
AB
Verhoef
J C
JC
Junginger
H E
HE
D000180:Acrylic Resins / Q000494:pharmacology*; D000269:Adhesives / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000097:blood / Q000493:pharmacokinetics*; D002064:Buserelin / Q000097:blood / Q000493:pharmacokinetics*; D002686:Chitin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048271:Chitosan; D004337:Drug Carriers; D004347:Drug Interactions; D005612:Freeze Drying; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000180:Acrylic Resins; D000269:Adhesives; D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D002686:Chitin; C006903:carbopol 940; D048271:Chitosan; D002064:Buserelin