Fenofibrate nano-suspension formulation using hot melt emulsion followed by precipitation

Abstract

Fenofibrate is a pharmaceutical drug of the fibrate class, which is used to lower abnormal lipid levels in the blood. However, fenofibrate suffers from poor bioavailability due to its hydrophobic nature and negligible water solubility. The generation of nanosuspension with increased surface area is one of the mechanisms to minimize this challenge. In this work, fenofibrate nanosuspension was formulated to improve the solubility of the drug. A method of hot melt emulsification followed by precipitating the hot melt into a cold aqueous medium was employed to generate the nanosuspension. Ultrasound energy and stabilizers such as Hydroxymethyl cellulose (HPMC), Polyvinyl Pyrrolidone (PVP), and Bovine Serum Albumin (BSA), along with surfactants including Tween 80 (T80) and Sodium Lauryl Sulphate (SLS), were used to control particle growth and improve the stability of the resulting suspension. Sunflower oil was used as a co-additive agent. The effects of surfactants, ultrasound energy and sonication time, drug to surfactant ratio, and sunflower oil on particle size and suspension stability were investigated. The use of ultrasound sonication during both the hot-melt formation step and the precipitation step produced smaller particle sizes. A ground mixture of fenofibrate with BSA and SLS, in the presence of 3 mL sunflower oil, produced a nanosuspension with particle sizes below 100 nm, exhibiting a relatively lower particle growth rate and improved stability. Using a lower molecular weight BSA surfactant and incorporating sunflower oil produced substantial improvement in the particle size reduction and enhancement of the suspension's stability.