Formulation optimization and PK/PD evaluation of novel valsartan bilosomes enhancing transdermal drug delivery

Abstract

RationaleThe skins capillary network makes it the bodys most accessible organ. However, the topmost layer of skin, known as stratum corneum (SC), is a substantial diffusional barrier for most drugs. It is suggested that edge activators (EAs) may provide the lipid bilayer of innovative elastic vesicles with ultra-flexibility that can penetrate SC employing high self-optimising deformability. It is fact that the therapeutic activity of lipophillic drugs can be improvized by incorporating novel formulations into the colloidal system. Aim and objectThe primary objective of this research work focused to formulation and optimization of novel bilosomes containing valsartan (VLT). MethodsThin film hydration (TFH) technique developed bilosomes in a 33-factorial design. Valsartan bilosomes (VLT-B) and valsartan bilosomal gels (VLT-BG) efficacy was assessed using ex vivo, in vitro and in vivo investigations. ResultsVLTBG had a higher area under the curve (AUC) and plasma concentration (Cmax) in the tested animals than the VLT oral solution. The optimised VLTB had 136.48 ± 7.82 nm diameter, −48.37 ± 0.49 mV of surface charge, and 88.56 ± 1.73 % of drug encapsulation. Oral VLT solution and VLT bilosomal gel Cmax were 52.37 and 215.39 μg/mL at 2 and 16 h, respectively. The AUC(0–∞) with the oral and transdermal application of the VLTBG was found to be 0.430 μg h/mL and 67.21 μg h/mL, respectively. ConclusionThe outcomes supported the hypothesis that bilosomes enhance VLT flow and concluded that the skin is better than the drug solution.