Formulation Development and Characterization of Lovastatin Nanogel for the Treatment of Hyperlipidemia

Abstract

Lovastatin (LS) is the cholesterol-lowering drug in the statin class, but it has poor oral bioavailability due to its high metabolism and low solubility, which affect its clinical efficacy. To overcome limitations associated with LS, the current study sought to develop a transdermal nanoemulsion using linseed oil and finally convert it into a nanogel formulation. Nanoemulsion (NE) was prepared using the spontaneous titration method. Different components of NE were selected based on solubility study and pseudo ternary phase diagrams were constructed using the titration method to determine the concentration range of components. Carbopol 934 was used to convert NE to nanogel (NG). The NE was selected based on the stability study and the composition of optimized NE consists of oil phase as 10%w/w linseed oil, 35%w/w Tween 80, and Polyethylene glycol 400 in 1:1 as Smix, and 55%w/w aqueous phase as water. The optimized NE (NE3) was characterized for various parameters and the formulation NE3 was found with desired globular size (108.9 ± 3.12 nm), polydispersity index 0.257 ± 0.015, zeta potential (−16.93 ± 1.12 mV), and spherical morphology. NE3 was combined with carbopol 934 to convert into NG and further characterized for pH, rheological behavior, and in vitro permeation study. The in vitro drug permeation study showed that the NG (33.69± 0.75 µg/cm2/hr) and NE (36.63± 0.55 µg/cm2/hr) have maximum permeation flux rate as compared to LS suspension (6.41±1.13 µg/cm2/hr). These results conclude that the NG formulation of LS can be a safe and effective alternative to an oral formulation of LS with enhanced permeation characteristics for transdermal delivery.