Venlafaxine loaded novasomes for intranasal delivery: Mucoadhesion, permeation and pharmacokinetics study

Depression is a mental disorder that often comes with symptoms like irritability, rage, changes in appetite or weight, hopelessness, and loss of interest in day-to-day activities. Venlafaxine (VLF) is a medication used to treat depression. When taken orally, only about 45 % of VLF enters the systemic circulation due to liver metabolism. However, if VLF is administered nasally, it can bypass the liver and be absorbed more efficiently. The nose has a strong blood supply and a high concentration of microvilli, which can speed up the absorption process and is not subject to first pass metabolism. To create a nasal spray for VLF, a combination of cholesterol, a nonionic surfactant, and a palmitic acid-lysine (PA-LYS) conjugation were used to make VLF-loaded novasomes. The optimal formulation, NPV3 consisted of cholesterol, brij35, and the PA-LYS conjugate. The size, surface charge, and PDI values of formulations ranged from 149 to 167 nm, -1.00 to -1.23 and 0.342 to 0.967, respectively. VLF was evenly and uniformly distributed within the novasomes, as indicated by the results of DSC and TGA investigations. The novasomes had adherence time of 7.9 h, with 65 to 95 % and 85.5 % VLF release and penetration, respectively. Compared to the commercially available Effexor® tablets, the trans-nasal injection of the NPV3 formulation resulted in a 1-fold increase in VLF bioavailability and an improved antidepressant effect. Therefore, the nasal delivery of VLF-loaded novasomes could be a significant improvement in the treatment of depression.