Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films

Abstract

To avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box–Behnken design was employed to optimize the permeation behavior of AVA from the transdermal film across the skin. The variables were the hydrophile-lipophile balance (HLB) of the surfactant (X1), the concentration of mixed micelles (MMs) in the film (X2), and the concentration of the permeation enhancer (X3). The initial permeation of AVA after 1 h (Y1), and the cumulative permeation of AVA after 24 h (Y2) were the dependent variables. Ex vivo studies were carried out on freshly isolated rat skin to investigate the drug’s permeation potential and results were visualized using a fluorescence laser microscope. Moreover, the pharmacokinetic behavior after a single application on male Wistar rats, in comparison with films loaded with raw AVA, was evaluated. The results showed that the optimum factor levels were 9.4% for the HLB of the surfactant used, and 5.12% MMs and 2.99% penetration enhancer in the film. Imaging with a fluorescence laser microscope indicated the ability of the optimized film to deliver the payload to deeper skin layers. Furthermore, optimized AVA-loaded TPGS-micelles film showed a significant increase (p < 0.05) in the Cmax of AVA and the area under the AVA plasma curve (approximately three-fold). The optimized AVA-loaded TPGS-MM film thus represents a successful delivery system for enhancing the bioavailability of AVA.

Transdermal Delivery of Glimepiride: A Novel Approach Using Nanomicelle-Embedded Microneedles

“…Transdermal drug delivery (TDD) presents an attractive alternative to conventional techniques due to its ease of accessibility, painlessness, self-administration convenience, and ability to bypass presystemic metabolism, which enhances bioavailability [ 12 ]. However, one obstacle in developing TDD systems is overcoming the natural transport barrier of the skin, which is the stratum corneum (SC) [ 13 ]. To enhance drug absorption, various active and passive technologies are employed, including passive techniques such as use of chemical enhancers and emulsions and active methodologies like ultrasound, velocity-based devices (powder or jet injectors), electrically operated methods (iontophoresis and electroporation), thermal assistance (such as radio-frequency heating and laser), and mechanical methodologies such as tape stripping and microneedles (MN) [ 12 ].…”