Shilpa Kakkar1, Indu Pal Kaur. 1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Abstract
CONTEXT: Ketoconazole, a lipophilic drug with a large molecular weight of 531.44 Da and a limiting aqueous solubility of 0.04 mg/ml is expected to show a poor transport across the skin. OBJECTIVE: The work describes usefulness of a novel, surfactant based elastic vesicular drug carrier system (SEVs), for enhanced dermal delivery. MATERIALS AND METHODS: The system constitutes Span 60 and an edge activator (Tween 80) and was characterized and monitored for safety and potential to target deeper mice skin layers. RESULTS: Nanosized (126 nm), elastic vesicles showed significantly high skin penetration and retention as compared to free drug suspension. Incorporation into different bases especially a hydrogel showed a significant retention which was even more than the market formulation (Nizral(®)). Safety was confirmed as cytotoxicity and acute dermal irritation/corrosion. Topically applied fluorescent vesicles labeled with 6-carboxyfluorescein, on mice skin, were observed intact in dermal layer 6 h post application. CONCLUSION: The results of the present study indicate that SEVs can be used to enhance skin delivery of the model high molecular weight and poorly water-soluble drug ketoconazole. The developed nanorange system is an effective system for targeting deeper mice skin layers which may be translated to human skin with suitable modifications, if required.
CONTEXT: Ketoconazole, a lipophilic drug with a large molecular weight of 531.44 Da and a limiting aqueous solubility of 0.04 mg/ml is expected to show a poor transport across the skin. OBJECTIVE: The work describes usefulness of a novel, surfactant based elastic vesicular drug carrier system (SEVs), for enhanced dermal delivery. MATERIALS AND METHODS: The system constitutes Span 60 and an edge activator (Tween 80) and was characterized and monitored for safety and potential to target deeper mice skin layers. RESULTS: Nanosized (126 nm), elastic vesicles showed significantly high skin penetration and retention as compared to free drug suspension. Incorporation into different bases especially a hydrogel showed a significant retention which was even more than the market formulation (Nizral(®)). Safety was confirmed as cytotoxicity and acute dermal irritation/corrosion. Topically applied fluorescent vesicles labeled with 6-carboxyfluorescein, on mice skin, were observed intact in dermal layer 6 h post application. CONCLUSION: The results of the present study indicate that SEVs can be used to enhance skin delivery of the model high molecular weight and poorly water-soluble drug ketoconazole. The developed nanorange system is an effective system for targeting deeper mice skin layers which may be translated to human skin with suitable modifications, if required.
Authors: Abdurrahman M Fahmy; Doaa Ahmed El-Setouhy; Ahmed B Ibrahim; Basant A Habib; Saadia A Tayel; Noha A Bayoumi Journal: Drug Deliv Date: 2018-11 Impact factor: 6.419