Transepithelial transport of ambroxol hydrochloride across human intestinal Caco-2 cell monolayers

Abstract

This study aimed i) to characterize the transepithelial transport of the mucolytic agent ambroxol hydrochloride across the intestinal barrier, ii) to classify the ambroxol according to Biopharmaceutics Classification System (BCS) and iii) to predict ambroxol absorption in humans. Transport of ambroxol (100, 300 and 1000 μmol/l) was studied in a human colon carcinoma cell line Caco-2 in apical to basolateral and basolateral to apical direction, under iso-pH 7.4 and pH-gradient (6 vs. 7.4) conditions. The relative contribution of the paracellular route was estimated using Ca 2+-free transport medium. Ambroxol samples from receiver compartments were analysed by HPLC with UV detection (242 nm). Results showed that ambroxol transport is linear with time, pH-dependent and direction-independent, displays non-saturable (first-order) kinetics. Thus, the transport seems to be transcellular mediated by passive diffusion. Estimated high solubility and high permeability (P app = 45 × 10-6 cm/s) of ambroxol rank it among well absorbed compounds and class I of BCS. It can be expected that the oral dose fraction of ambroxol absorbed in human intestine is high.

Steroid/mucokinetic hybrid nanoporous microparticles for pulmonary drug delivery

“…The formation of nanopores and the increase in the specific surface area in the presence of (NH 4 ) 2-39 CO 3 were mainly attributed to the neutralisation of ambroxol-HCl to form ambroxol base. Thus, ambroxol 40 base could behave in the same manner as budesonide and prompt nanoprecipitation when spray dried 41 from an ethanol/water mix occurs. All formulations were amorphous, which should enhance dissolution 42 rate and diffusion through lung fluid.…”

Microsphere formulations of ambroxol hydrochloride: influence of Okra (Abelmoschus esculentus) mucilage as a sustained release polymer

“…In vitro dissolution test of ambroxol hydrochloride from the Okra mucilage-based microspheres were carried out in phosphate buffer media, pH 6.8, to simulate the physiological conditions in the small intestine, being the site that was targeted for drug release. According to Stetinová et al (2009), the high solubility and high permeability of ambroxol hydrochloride rank it among well-absorbed compounds and class I of BCS, Therefore, the oral dose fraction of ambroxol absorbed in human intestine is expected to be high. Figure 5 shows cumulative percentages of ambroxol released against time.…”

Ambroxol, a mucolytic agent, boostsHO‐1, suppressesNF‐κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis

“…29 Transepithelial transport of ambroxol through Caco-2 cell monolayers proposed that its oral dose fraction absorbed from the human intestine is high. 30 In addition, Weiser 31 reported the 14 C-labeled ambroxol tissue distribution of radioactivity in rats, after 3 h of oral dosage of 14 C-labeled ambroxol, radioactivity was revealed primarily in the lungs, intestines, kidneys, and liver. Ambroxol hydrochloride anti-oxidant and anti-inflammatory effects have not yet been investigated in ulcerative colitis.…”