Penetration enhancers-containing vesicles for "Terbinafine HCl" skin delivery

Abstract

Skin is an important organ that acts as a protective barrier against foreign materials through its multilayered structure. It also prevents the loss of endogenous materials such as water. Drug delivery through the skin either targets the dermal layer or goes deeper to the systemic circulation. Dermal delivery is only used to treat dermatological conditions such as skin cancer, psoriasis, eczema, and microbial infections with minimal systemic uptake. This allows for avoidance of first pass metabolism and other gastrointestinal symptoms associated with some medications. This will then improve the therapeutic values for active agents and improve patient drug acceptance. However, low skin penetration is always a limiting factor for the skin delivery of the therapeutic moieties. This is the challenging point that scientists tried to overcome through both physical and chemical methods. Among the successful chemical methods for dermal drug delivery are nanocarriers. Numerous lipid based delivery systems have been developed starting with liposomes. Liposomes are nano-sized vesicles that could hardly permeate the uppermost layers of the skin. Several modifications were done to the vesicular membrane in order to enhance drug delivery deeper into skin layers. Flexible vesicles, named transfersomes, were then developed containing an edge activators which allow vesicles to squeeze through skin layers. Another type of vesicles is ethosomes, in which ethanol is incorporated in the phospholipid membrane, this allows for both higher penetration power plus superior flexibility than liposomes. Moreover, different successful delivery systems were developed using Summary 170 different classes of penetration enhancers. Those vesicles were able to deliver different hydrophilic and lipophilic drug models deep into skin layers. Thanks to the synergistic action between different penetration enhancers as well as phospholipids. TBN HCl is a lipophilic allylamine antifungal drug that can act topically or orally as fungistatic and fungicidal. Oral TBN HCl has been shown to be effective in the treatment of onychomycosis and Tinea capitis. On contrary, Tinea pedis/cruris/corporis were recommended to be treated by topical TBN HCl. Oral administration of TBN HCl caused mild to moderate gastrointestinal adverse effects. The aim of this work was to maximize the efficiency of topical TBN HCl delivery and decrease the treatment duration for Tinea pedis using vesicular systems approach. Hence the work in this thesis was divided into 4 chapters. Chapter one: Development of HPLC method for TBN HCl determination Chapter two: Preparation and characterization of TBN HCl loaded vesicles. Chapter three: Preparation and characterization of TBN HCl vesicular gels. Chapter four: In vivo evaluation of TBN HCl loaded vesicles and vesicular gels.