Implementing Spanlastics for Improving the Ocular Delivery of Clotrimazole: In vitro Characterization, Ex vivo Permeability, Microbiological Assessment and In vivo Safety Study

Purpose: The aim of this study was to encapsulate clotrimazole (CLT), an antifungal drug with poor water solubility characteristics, into spanlastics (SPs) to provide a controlled ocular delivery of the drug. Methods: Span 60 was used in the formulation of SPs with Tween 80, Pluronic F127, or Kolliphor RH40 as an edge activator (EA). The presence of EA offers more elasticity to the membrane of the vesicles which is expected to increase the corneal permeation of CLT. SPs were prepared using ethanol injection method applying 3(2) complete factorial design to study the effect of formulation variables (ratio of Span 60: EA (w/w) and type of EA) on SPs characteristics (encapsulation efficiency percent (EE%), average vesicle size (VS), polydispersity index (PDI) and zeta potential (ZP)). Design-Expert software was used to determine the optimum formulation for further investigations. Results: The optimum formulation determined was S1, which contains 20 mg of Tween 80 used as an EA and 80 mg of Span 60. S1 exhibited EE% = 66.54 +/- 7.57%, VS = 206.20 +/- 4.95 nm, PDI = 0.39 +/- 0.00 and ZP = -29.60 +/- 0.99 mV. S1 showed highly elastic sphere shaped vesicles. Furthermore, S1 displayed a sustained release profile and a higher ex vivo permeation across rabbit cornea relative to CLT suspension. Also, S1 revealed superior inhibition of Candida albicans development compared to CLT suspension applying 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction technique. Moreover, in vivo histopathological examination assured the safety of S1 after ophthalmic application in mature male albino rabbits. Conclusion: Overall, the outcomes revealed the marked efficacy of SPs for ocular delivery of CLT.

Automated summary

This study aimed to encapsulate the antifungal drug clotrimazole (CLT) into spanlastics (SPs) to provide controlled ocular delivery. The optimal formulation S1 showed high encapsulation efficiency, elastic vesicles, sustained release profile, and superior inhibition of Candida albicans development compared to CLT suspension. In vivo histopathological examination confirmed the safety of S1 for ophthalmic application in rabbits, demonstrating the efficacy of SPs for ocular delivery of CLT.