Hydroxypropyl-beta-cyclodextrin: A Novel Transungual Permeation Enhancer for Development of Topical Drug Delivery System for Onychomycosis

The treatment of onychomycosis is a challenging task because of unique barrier properties of the nail plate which hampers the passage of antifungal drugs in a concentration required to eradicate the deeply seated causative fungi in the nail bed. In present investigation, application of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was established as an effective and nail friendly transungual drug permeation enhancer especially for poorly water soluble drugs using terbinafine hydrochloride as a poorly soluble drug. HP-beta-CD significantly improves hydration of nail plates and increases solubility of terbinafine hydrochloride in the aqueous environment available therein, which leads to uninterrupted drug permeation through water filled pores of hydrogel-like structure of hydrated nail plates. A nail lacquer formulation was designed with an objective to deliver the drug in an effective concentration across nail plates, using HP-beta-CD as a permeation enhancer. The formulations containing HP-beta-CD showed higher flux than the control formulation in in vitro drug permeation study. The formulation containing 10% w/v of HP-beta-CD showed maximum flux of 4.586 +/- 0.08.. g/mL/cm(2) as compared to the control flux of 0.868 +/- 0.06 rho g/mL/cm(2). This finding supports application of HP-beta -CD as an effective permeation enhancer for transungual delivery of terbinafine hydrochloride and possibly other poorly water soluble drugs where HP-beta-CD can act as a solubilizer.