International Journal of Pharmaceutics 327 (2006) 139–144 Preparation of nanomagnetic absorbent for partition coefficient measurement Shik Chi Tsang a,∗ , Chih Hao Yu a , Xin Gao a , Kin Y. Tam b a The Surface and Catalysis Research Centre, School of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK b AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK Received 11 March 2006; received in revised form 11 May 2006; accepted 12 July 2006 Available online 22 July 2006 Abstract In this paper, we report a new method based on supercritical carbon dioxide (scCO 2 ) to fill and distribute the porous magnetic nanoparticles with n-octanol in a homogeneous manner. The high solubility of n-octanol in scCO 2 and high diffusivity and permeability of the fluid allow efficient delivery of n-octanol into the porous magnetic nanoparticles. Thus, the n-octanol-loaded magnetic nanoparticles can be readily dispersed into aqueous buffer (pH 7.40) to form a homogenous suspension consisting of nano-sized n-octanol droplets. We refer this suspension as the n-octanol stock solution. The n-octanol stock solution is then mixed with bulk aqueous phase (pH 7.40) containing an organic compound prior to magnetic separation. The small-size of the particles and the efficient mixing enable a rapid establishment of the partition equilibrium of the organic compound between the solid supported n-octanol nano-droplets and the bulk aqueous phase. UV–vis spectrophotometry is then applied to determine the concentration of the organic compound in the aqueous phase both before and after partitioning (after magnetic separation). As a result, log D values of organic compounds of pharmaceutical interest determined by this modified method are found to be in excellent agreement with the literature data. © 2006 Elsevier B.V. All rights reserved. Keywords: Magnetic nanoparticle; Porous; Supercritical fluid; Partition coefficient; Magnetic separation 1. Introduction A new nanotechnology based on magnetic separation using nanomagnet has recently been explored (Nam et al., 2003). This can be described as a two-step process, involving (i) tagging or labeling of desired biological/chemical entity on colloid mag- netic nano-particle for recognition of complementary species in solution, and (ii) separation of the resulting solid entities via a fluid-based magnetic separation followed by regeneration of the species from the particle. The technique is now widely adopted in protein purification, immunoassays, pre-processing in polymerase chain reactions and pre-concentration of biolog- ical entities. Recently, applications of magnetic separation to catalysis and bio-catalysis areas in order to regenerate expen- sive catalyst species (Tsang et al., 2004) or enzymes (Gao et al., 2003) from reaction mixture have been particularly noted. On ∗ Corresponding author. Tel.: +44 118 3786346; fax: +44 118 3786632. E-mail address: s.c.e.tsang@reading.ac.uk (S.C. Tsang). the other hand, there is very limited work of this new technique to seek applications to pharmaceutical industry. For screening lead compounds in pharmaceutical industry, lipophilicity is a useful physicochemical parameter reflecting the transfer properties of a compound across biological membranes (Comer et al., 2001; Leo et al., 1969). This can be described by the n-octanol/water partition coefficient (log D), which is defined as the ratio of concentrations of a compound in all its forms between an aqueous phase (buffer) and an n-octanol phase. Shake-flask method is a simple and traditional method for the determination of the log D value (Comer et al., 2001; Leo et al., 1969). It is accepted as a standard procedure by the Organ- isation for Economic Cooperation and Development (OECD, 1992). The compound is introduced into the two immiscible phases, n-octanol and aqueous buffer solution, in a separator funnel. The funnel is then shaken until the partitioning equilib- rium is achieved. After phase separation the concentration of the compound in each phase was determined. The drawbacks of this method include: a slow partitioning because of the bulk phases involved, labor intensive and emulsion formation upon shaking 0378-5173/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2006.07.031