Objective: The objective of the present study was to design topical Nanoemulsion based gel of Terbinafine HCl, a poorly soluble drug, to increase its permeability and evaluate its efficacy in an animal model.
Materials and Methods: Nanoemulsions were incorporated into gels and designated as Gel-P and Gel-S respectively. Nanoemulsion gel was prepared using liquid paraffin, glycerin, and carbomer 940. Nanoemulsions were prepared by two different techniques viz. high pressure homogenization and high speed homogenization. The developed gels were evaluated for drug content, spreadability, microbial assay and in vitro permeation using pork skin. The in vivo antifungal efficacy of the developed gels was assessed in albino Wistar rats.
Results and Discussion: The globule size obtained by high pressure homogenization was less than 2 r.nm (nanometer in radius) and that by high speed homogenization was less than 10 r.nm. In vitro permeation studies revealed that Gel-P (51.19±0.81 %) had higher permeation when compared to Gel-S (31.72±1.12 %) and marketed cream (19.78±1.01 %) which is essential to treat topical fungal diseases. In vivo antifungal studies in Wistar rats infected with Trichophyton mentagrophytes revealed that topical application of Gel P and Gel S cured the infection within 3 d compared to 14 d for marketed cream.
Conclusion: This study confirms that the Nanoemulsion gels provided greater permeation followed by cure rates of poorly soluble Terbinafine HCl in animal model and hence these systems could be the preferred drug carriers for drugs intended for topical use to overcome the permeability and efficacy problems.
Keywords: Terbinafine HCl, Nanoemulsion gel, permeability, poorly soluble drug, Topical antifungal, Trichophyton mentagrophytes.
The development of dosage forms for topical drug delivery is one among the many challenging areas to the formulation scientist. Among the various layers of skin (i.e. epidermis, dermis and hypodermis), the stratum corneum of epidermis is the effective rate limiting barrier to percutaneous drug transport, as this layer is made up of dead cells of corneocytes which lack nuclei and organelles . Due to its unusual composition (40% proteins, 40% lipids and 20% water) and tight intercellular junctions (corneodesmosomes), the stratum corneum is the most formidable barrier when compared to the other epithelial barriers of gastrointestinal, rectal, buccal, nasal and vaginal routes. Majority of new chemical entities (approx. 40% of the drugs) currently being synthesized in R&D are lipophilic in nature .They show wetting difficulties and poor dissolution, eventually leading to poor penetration [4,5]. These properties present a rate-limiting step in their topical permeation and in turn cause a subsequent reduction in their efficacy. Whenever a drug is applied to the skin, whether poorly or highly soluble, only a small fraction of applied drug is able to penetrate from...