The purpose of this study was to investigate the intestinal and nasal absorption enhancement of cefotaxime (CTX) by ion-pairing with counterions and to design an effective oral and intranasal delivery system for antibiotics. Counterions for
absorption
promotion were cationic surfactants [cetylpyridinium chloride (CP), cetrimide (CT) and benzalkonium chloride (BA)]. In the presence of counterions, the apparent partition coefficient of cefotaxime was increased depending on the molar
concentration
of
the counterions. Anion interference was observed for ionpairing of cefotaxime with counterions because of the counterbalance between an anion and counterions. The preset study employed the in situ simultaneous nasal and intestinal perfusion
technique in
rats. The apparent permeabilities(Papp) of cefotaxime were 1.43±0.04×1005cm/sec(mean±SE) in the nasla cavity and 0 in the jejunum, respectively, which indicated that the intrinsic absorptivity of cefotaxime was greater in the nasal cavity than
in the
jejunum, When ionupairing formers were used, the decreasing order of apparent cefotaxime permeability (Papp. 10-5 cm/sec), corrected for surface area of absorption, was as followings; BA (7.50±0.36)>CT (4.92±0.24)>CP(3.01±0.17) in the jejunum
and BA
(22.31 1.36)> CP (18.24±0.81)> CT (16.22±1.87) in the nasal cavity. The increase in permeability of cefotaxime was about 13-fold in the rat nasal cavity and was marked in the rat jejunum for ion-pairing with counterions as compared to those
without
ion-pairing. The damages of jejunal and nasal nasal mucosal membrane by counterions were observed within approximately 2hrs after removal of ion-pair of cefotaxime with counterions from the nasal cavity and jejunum. These results results suggest
that CP
can be used as an ion-pairing former in the jejunum and CP and CT can be used as ion-pairing formers in the nasal cavity for cefotaxime, as well as for poorly absorbed drugs with a negative charge due to ionization.
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