Optimization and evaluation of amoxicillin medium chain fatty acids/salts microemulsions: intestinal absorption and cytotoxicity

Pseudoternary microemulsions have been developed which, in addition to non-ionic medium-chain glycerides and fatty acids such as caprylic (C 8) and capric acids (C 10), incorporate ionic lipids, i.e. the sodium salts of fatty acids. The permeability, absorption enhancing activity were evaluated using phenol red as a marker molecule and the cytotoxicity of these lipid microemulsions were investigated in rats by measuring the amount of proteins and lactate dehydrogenase enzyme released in the intestinal fluids. The histopathological follow up of colonic membranes after administration of microemulsions was used to assess tissue damage. In vitro permeability and absorption studies showed that caprate-based systems containing captex 200 (20%), surfactant mixture of polysorbate 80: sodium caprate 4:1 (60%), capmul MCM C 8: capric acid 1:1(20%) significantly (P < 0.05) increased the permeability of phenol red compared to other microemulsion systems with 4 times improved colonic absorption. Paracellular absorption was the suggested enhancing mechanism where no good correlation could be found between the AUC of phenol red and the amounts of lactate dehydrogenase or proteins released in the presence of incorporated permeation enhancers. Intracolonic administration of caprate microemulsion containing only 80 mg amoxicillin was able to deliver amoxicillin in enhanced time (11 min) and concentration (9.85 μg/mL) compared with a commercial product containing 500 mg amoxicillin with unaltered membrane integrity. This supports the short-term use of these microemulsion formulations to improve the intestinal absorption of water-soluble low permeable compounds without any toxicity concerns.