A fastHigh Performance Liquid Chromatography (HPLC) method was developed and validated for the simultaneous quantitative determination of phenylbenzimidazole sulfonic acid (PBMSA), benzophenone-3 (BZ3), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), octocrylene (OC), butyl methoxydibenzoylmethane (BMBM), ethylhexyl methoxycinnamate (EMC), ethylhexyl salicylate (ES), and homosalate (HS) which are eightorganic UV-filters of the most commonly used in cosmetics and sunscreens. A solution pH 2.0 of phosphate buffer, methanol, and acetonitrile in proportions 15:3:82 respectively as mobile phase was used in isocratic conditions, combined with a Purospher Star ® Performance RP-18e column and eight minutes of analysis time. The proposed method was validated following the recommendations of International Council on Harmonization (ICH) and the Food and Drug Administration (FDA) guidelines. All parameters examined were found to be well within the stated guidelines. From the robustness test, it was possible to identify that pH of the buffer and the vial material are the critical methodological parameters for the analysis of butyl methoxydibenzoylmethane (BMBM), whereas for phenylbenzimidazole sulfonic acid (PBMSA) they were, the vial material, volume ofNaOH solution and sonication time and temperature.
The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5'-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.
