Thiolated alkyl-modified carbomers: Novel excipients for mucoadhesive emulsions

The aim of this study was the design and evaluation of mucoadhesive emulsifying polymeric excipients. Three thiol bearing ligands with increasing pKa values of their sulfhydryl group, namely 4-aminothiophenol (pKa = 6.86), l-cysteine (pKa = 8.4) and d/l-homocysteine (pKa = 10.0) were coupled to the polymeric backbone of alkyl-modified carbomer (PA1030). Resulting conjugates displayed 818.5 μmol 4-aminothiophenol, 698.5 μmol cysteine and 651.5 μmol homocysteine per gram polymer and were evaluated regarding the reactivity of thiol groups, emulsifying and mucoadhesive properties. In general, the synthesized conjugates showed a pH dependent reactivity, whereby the fastest oxidation occurred in PA1030-cysteine, as almost no free thiol groups could be detected after 120 min. Emulsification of medium chain triglycerides was feasible with all synthesized conjugates leading to oil-in-water-emulsions. Emulsions with PA1030-cysteine displayed the highest stability and the smallest droplet size among the tested formulations. Oxidation and consequently cross-linking of the thiomers prior to the emulsification process led to an overall decreased emulsion stability. Evaluating mucosal residence time of thiomer emulsions on porcine buccal mucosa, a 9.2-fold higher amount of formulation based on PA1030-cysteine remained on the mucosal tissue within 3 h compared to the unmodified polymer. According to these results, the highest reactive ligand l-cysteine seems to be most promising in order to obtain thiolated polymers for the preparation of mucoadhesive o/w-emulsions.

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