Clove Oil Endorsed Transdermal Flux of Dronedarone Hydrochloride Loaded Bilosomal Nanogel: Factorial Design, In vitro Evaluation and Ex vivo Permeation

Abstract

The goal of this study was to develop a bilosomal gel formulation to enhance transdermal permeability of dronedarone hyrdrochloride (DRN) which suffers from poor oral absorption and limited bioavailability. To overcome this obstacle, bilosomes were successfully prepared using 23 full-factorial design. Span®40, cholesterol, sodium deoxycholate (bile salt), clove oil (permeability enhancer), and either Tween® 60 or Tween® 80 (edge activator) were used in bilosome preparation by ethanol injection method. In this design, independent variables were X1, edge activator type; X2, edge activator amount (mg); and X3, permeability enhancer concentration (% w/v). Optimal formula (B2) of the highest desirability of (0.776) demonstrated minimum vesicle size (VS) of 312.4 ± 24.42 nm, maximum absolute value of zeta potential (ZP) − 36.17 ± 2.57 mV, maximum entrapment efficiency (EE %) of 80.95 ± 3.01%, maximum deformability Index (DI) of 8.24 ± 1.26 g and maximum drug flux after 12 h (J12) of 21.23 ± 1.54 µg/cm2 h upon ex vivo permeation study. After 12 h, 70.29 ± 6.46% of DRN was released from B2. TEM identification of B2 showed spherical shaped nanosized vesicles which were physically stable for 3 months at different temperatures. B2 was incorporated into carboxymethylcellulose gel base for easiness of dermal application. B2 gel demonstrated good physical properties, non-Newtonian psuedoplastic flow, and enhanced release (57.0 ± 8.68% of DRN compared to only 13.3 ± 1.2% released from drug suspension after 12 h) and enhanced skin permeation. Graphical abstract

Emerging Trends in Bilosomes as Therapeutic Drug Delivery Systems

“…Another poor orally bioavailable drug, dronedarone hydrochloride (DRN), was also formulated into bilosomal nanogel to enhance transdermal permeability and bioavailability. The optimized bilosomal gel formula demonstrated an in vitro drug release of 57.0 ± 8.68% relative to 13.3 ± 1.2% from drug suspension after 12 h. The ex vivo permeation study findings showed an enhanced skin permeation of 21.23 ± 1.54 µg/cm 2 h across rat skin and collectively showed the superior efficacy of bilosomal gel compared to free drug suspension [ 75 ].…”

Development of Transdermal Oleogel Containing Olmesartan Medoxomil: Statistical Optimization and Pharmacological Evaluation

“…Prior to starting the experiment, the frozen skin was thawed till reaching room temperature. This study was implemented utilizing the USP dissolution apparatus II by applying the same conditions utilized in the in vitro drug release study [33,34]. The newly born rat skin was fixed on the glass cylinder having a surface area of 4.908 cm 2 .…”

The Exploitation of Sodium Deoxycholate-Stabilized Nano-Vesicular Gel for Ameliorating the Antipsychotic Efficiency of Sulpiride

“…In addition, bile salts greatly reduce the temperature at which lipids undergo phase transition, resulting in bilosomal vesicles that are extremely deformable and flexible at physiological temperature. The flexibility of bilosomal vesicles greatly facilitates transdermal application through enhancing penetration into the skin's deep layers [23]. Significantly, the presence of bile salts, sodium deoxycholate (SDC), greatly improves the stability of bilosomal vesicles, in comparison to other traditional vesicles [24].…”