Research Article: Distribution of benzalkonium chloride into the aqueous phases of submicron dispersed systems: emulsions, aqueous lecithin dispersion and nanospheres

Date Published: December 2, 2019

Publisher: Springer International Publishing

Author(s): Dorota Watrobska–Swietlikowska.

http://doi.org/10.1208/s12249-019-1540-7

Abstract

Partitioning of benzalkonium chloride (BAC) into the aqueous phases of submicron dispersed systems such as submicron emulsions, aqueous lecithin dispersion (WLD), and suspension of nanospheres (NLC) was studied. The aqueous phases of the investigated systems were obtained by ultracentrifugation and subsequently were subjected to ultrafiltration, which procedure allowed distinguishing between the fractions of free benzalkonium chloride (w) and those incorporated in the liposomal and micellar region (wlm). The fractions present in the oily phase and in the interphase of submicron emulsions were calculated. Despite the various composition of the investigated formulations and the initial concentration of BAC, w values were very small at 0.2–8.0%. The wlm value in submicron emulsions was increased by increasing the total concentration of preservative from 29.0 to 42.0%. Using polysorbate 80 instead of lecithin resulted in a distribution of BAC to aqueous–liposomal–micellar phase that was twice as high. The very low concentration of antimicrobial active form of benzalkonium chloride was analyzed in the aqueous phase of emulsions stabilized with lecithin as well as in aqueous lecithin dispersion and nanospheres (below 3%). Replacement of lecithin with polysorbate 80 in emulsions with polysorbate significantly increase (up to 8%) the fraction of benzalkonium chloride in the aqueous phase where microbial growth occurs.

Partial Text

Pharmaceutical and cosmetic products that contain the aqueous phase should be properly preserved against microbial contamination and proliferation during storage in normal conditions and proper use (1).

Modern submicron dispersed systems such as submicron emulsions, which are already used as drug carriers, as well as potential drug carriers aqueous lecithin dispersions (WLD) and suspensions of lipospheres (nanostructured lipid carriers, NLC), were the subject of the presented studies. The characteristic of investigated submicron systems is the presence of phospholipids of lecithin, which in submicron emulsions cover liquid lipid–soya bean oil and in aqueous lecithin dispersions build microparticles with unknown internal structure was evaluated. Aqueous lecithin dispersions differ from submicron emulsions in the lack of oily phase. Nanostructured lipid carriers (lipospheres) consist of solid lipid and different emulsifier—C8–C16 fatty alcohol polyglycoside (PlantaCare 2000). Emulsions stabilized with polysorbate 80 instead of lecithin were studied to compare the influence of phospholipids on the distribution of BAC between phases of submicron emulsion. To investigate the internal structures of the types of dispersions and to compare the influence of the composition on the nanostructure of the dispersed phase, a cryo-electron transmission microscope was used and the results were presented in my previous work (24). It should be noted that microscopic examinations confirmed the results obtained during instrumental size determinations by the PCS method. The smallest in size and most uniform were vesicles suspended in the WLD formulation. Regardless of the differences in the composition of the emulsions, their microscopic images revealed the presence of particles of 2 types: oil droplets (dark spheres) and vesicles (mainly SUV), which number depended on the lecithin content. Replacement of lecithin with polysorbate 80 resulted in a decrease in the number of small liposomes in the formulation.

The very low concentration of the antimicrobial active form of benzalkonium chloride was analyzed in the aqueous phase of emulsions stabilized with lecithin as well in aqueous lecithin dispersion and nanospheres. Replacement of lecithin with polysorbate 80 in emulsions with polysorbate significantly increased the fraction of benzalkonium chloride in the aqueous phase where microbial growth occurs. BAC can be a potential effective preservative in emulsion stabilized with polysorbate 80, which requires the effectiveness of the antimicrobial preservation test.

 

Source:

http://doi.org/10.1208/s12249-019-1540-7

 

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