Dense nanolipid fluid dispersions comprising ibuprofen: Single step extrusion process and drug properties

Abstract

Dense nanolipid fluid (DNLF) dispersions are highly concentrated aqueous dispersions of lipid nanocarriers (LNCs) with more than 10¹⁵ lipid particles per cubic centimeter. Descriptions of dense nanolipid fluid dispersions in the scientific literature are rare, and they have not been used to encapsulate drugs. In this paper we describe the synthesis of DNLF dispersions comprising ibuprofen using a recently described twin-screw extrusion process. We report that such dispersions are stable, bind ibuprofen tightly and yet provide high transdermal drug permeation. Ibuprofen DNLF dispersions prepared according to the present study provide up to five times greater flux of the pharmacologically active S-ibuprofen isomer through human skin than a commercially available racemic ibuprofen emulsion product. We demonstrate scaling up the twin-screw extrusion method to pilot production for a stable, highly permeating ibuprofen DNLF composition based on excipients approved by the US FDA for use in topical products as a key step towards development of a commercially viable, FDA approvable topical ibuprofen medicine to treat osteoarthritis, which has never before been accomplished.

Keywords: Dermal permeation; Hot-melt extrusion; Ibuprofen; Lipid nanocarriers; Nanoparticles; Topical drug delivery; pH stat titration drug release method.