1. Introductiona b s t r a c tProdu

1. Introduction
a b
s
t r a c t
Production
of active
b
ingredients such as pharmaceuticals in nano-particulate form is highly desirable but the resulting product is difficult to handle and to use in applications. A novel process is described for coating
nanoparticles onto excipient particles of c. 300  m by rapid expansion of a supercritical solution (RESS) into two types of modified proprietary equipment: a Wurster coater and a fluidized bed. This novel approach has
been demonstrated through the successful deposition of six mimics for active ingredients (benzoic acid, adamantane, ferrocene, phenanthrene, stearic acid and vitamin K3) on carrier excipient particles
of microcrystalline cellulose (MCC). Evidence from SEM, EDX and Confocal Raman microscopy suggests that the coating particles are below 30 nm in size. Unlike most conventional coating processes, this
approach
avoids the use of liquids and high temperatures. As a wide range of actives and excipients can potentially be employed, the approach is applicable across the process and product industries, in particular pharmaceutical, household goods, personal care and catalyst industries.
© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/3.0/ ).
Active ingredients in nanoparticulate form can have advantageous properties; for example, nanoparticulate drugs can show higher bioavailability [1] and catalysts higher activity [2]. Nanoparticulates are not readily attainable through conventional crystallization routes and a subsequent comminution stage is often necessary, which may disadvantageously alter the physicochemical properties of the product. In principle, supercritical processes are more attractive because they can deliver a narrow particle size distribution [3,4], consist of only one process step, do not require liquid solvents and can be undertaken at moderate temperatures. A further advantage is that they offer control over solid state properties, producing either amorphous or crystalline material and sometimes polymorphs which are not obtainable by other means [5,6].
The supercritical particle formation process used here is rapid expansion of supercritical solutions (RESS), in which the solution is expanded through a constriction, resulting in a very rapid pressure decrease, high supersaturation and rapid precipitation of fine particles. There are numerous reports describing the production of nanoparticles via this method [7–12]. However, since even van der Waals’ forces between particles of 1  m far exceed