Thin layer chromatographic compatibility study in preformulation of new transdermal therapeutic systems

Objective: The compatibility of four binary active substances combinations adapalene – levofloxacin (ADP-LFX), adapalene – miconazole nitrate (ADP-MCZ), levofloxacin – meloxicam (LFX-MLX) and levofloxacin – miconazole nitrate (LFX-MCZ) was analysed to be comprised in new transdermal therapeutic systems. Also, the compatibility of selected active substances and four polymeric excipients (hydroxypropyl methyl-cellulose - HPMC 15000, hydroxypropyl methylcellulose - HPMC E5, ethyl cellulose - EC 10, and hydroxyethyl cellulose – HEC) was studied.

Methods: Thin layer chromatographic method (TLC) and four selected mobile phases were used. On the plate (in situ) were obtained the binary combinations (active substances and active substance-polymer).

Results: A good compatibility of ADP-LFX was found using ammonia : methanol : acetonitrile : methylene chloride 2:4:1:4 mobile phase. Using chloroform : acetone : glacial acetic acid 34:4:3 on the chromatogram of ADP-MCZ, only ADP spots appeared but without changes in the shape of the spots and R_f values. Any modifications of LFX and MLX spots (from LFX-MLX mixture) had been observed using toluene : glacial acetic acid : methanol 11:1:0.5 mobile phase, although LFX spots have remained on the baseline. Only LFX spots were visible from LFX-MLX and LFX-MCZ mixtures (ammonia : methanol : acetonitrile : methylene chloride 2:4:1:4 mobile phase). Distinctive spots were observed for ADP, LFX and MLX with variable results from no chemical interactions to limited chemical interactions when the compatibility with polymers was verified.

Conclusions: ADP-LFX and LFX-MLX mixtures were found to be compatible. ADP with HPMC polymers and LFX with HPMC E5 and HEC had presented excellent compatibility; for the other binary combinations, different analytical methods will be necessary.