Optimization and characterization of sertaconazole nitrate flexisomes embedded in hydrogel for improved antifungal activity

Abstract

The aim of the present research work was to develop, characterize and optimize sertaconazole nitrate (STZN) embedded flexisomes (STZN-FS) to improve the cutaneous anti-fungal activity of STZN. Flexisomes are self-aggregating, flexible, deformable lipidic vesicles possessing an aqueous core. A 3² factorial design was implemented to optimize the effects of the critical material attributes of concentration of phospholipid (X₁) and edge activator (X₂) on the critical quality attributes of particle size (Y₁), entrapment efficiency (Y₂), and deformability index (Y₃). Statistical analysis was performed to be identify the best fit model and determine its significance. The sizes of the optimized STZN-FS were found to be 246.2 ± 2.49 nm with entrapment efficiencies of 86.16 ± 0.56% and deformability indices of 30.46 ± 0.41. Zeta potential analysis showed negatively charged surface with a zeta potential value of −30.9 mV. TEM analysis showed spherical shapes, confirming the vesicular characteristics. The optimized STZN-FS were further formulated into hydrogels. The % drug diffusion of STZN-FS hydrogels was found to be 13.24% and drug deposition in the skin layers was found to be 83.54%, showing that a high concentration of the drug was available at the site of action. The zone of inhibition STZN-FS hydrogel (30 mm) was higher than the marketed formulation (22 mm) and the plain STZN hydrogel (14 mm) against Candida albicans. From the above studies, it was concluded that STZN loaded STZN-FS shows high flexibility and enhanced antifungal activity. STZN-FS are thus found to be potential carriers for drug deposition in skin layers without disturbing their integrity.

Keywords:

• Flexisomes
• sertaconazole nitrate
• hydrogel
• factorial design
• antifungal activity

Acknowledgement

Authors are grateful to Lipoid GmbH Ludwigshafen, Germany for providing gift sample of Lipoid S75 and NCIM, National Chemical Laboratory, Pune for providing Candida albicans culture. Authors are thankful to SAIF, Indian Institute of Technology, Bombay and Department of Histopathology, Smt. Kashibai Navale Medical College and Hospital, Pune for kind assistance and help in carrying out TEM studies and histopathology studies, respectively.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.