NAVNEET BHULLI, ARVIND SHARMA
ABSTRACT
Glimepiride is a third generation sulfonylurea antidiabetic drug. It is practically insoluble in water; this poor aqueous solubility and slow dissolution may lead to irreproducible clinical response or therapeutic failure due to sub therapeutic plasma drug levels. Low oral bioavailability results in wasting of a large portion of an oral dose. To circumvent these drawbacks glimepiride was entrapped in novel vesicular carrier system (Ethosomes) to improve therapeutic efficacy of glimepiride via transdermal route. Therefore current work was aimed to formulate, characterize and evaluate the transdermal potential of ethosomes encapsulating glimepiride. Vesicular shape, surface morphology and entrapment efficiency were determined by optical microscopy, transmission electron microscopy, and minicolumn centrifugation technique respectively. In contrast to liposomes, ethosomes were of more condensed vesicular structure and they were found to be oppositely charged. The ethosomal formulation were found to be more efficient delivery carriers with high entrapment and optimal nanometric size range and low polydispersity index in comparison with plain drug solution and liposomal formulation. The ethosomal formulations exhibited entrapment efficiencies of 42–78%. In vitro percutaneous permeation experiments demonstrated that the permeation of glimepiride through rat skin was significantly increased when ethosomes were used. Kinetics of in-vitro skin permeation showed zero order drug release from formulations. The flux from ethosomes was 3-fold higher than liposomal solution. FT-IR studies revealed that when skin was treated with ethosomal formulation ceramides got loosened leading to breaking of hydrogen bond networks at the head of ceramides due to penetration of ethosomal into the lipid bilayers of SC. Results suggested ethosomes to be the most proficient carrier system for dermal and transdermal delivery of glimepiride.
KEYWORDS: Ethosomes, invitro percutaneous permeation, sustained release, glimepiride