(616a) Interfacial Stability: Polymeric Nanoparticles of Itraconazole and Odanacatib

Polymeric nanoparticles (NPs) are used as vehicles for hydrophobic drug delivery [1,2]. Amphiphilic block copolymers stabilize the hydrophobic drug core during the rapid precipitation process of nanoparticle formation [3]. The stability of formulated nanoparticles is largely governed by Ostwald ripening [4,5].

The successful formulation of itraconazole and odanacatib into nanoparticle form with diameters of 145 nm and 350 nm, respectively, using rapid, block copolymer-directed precipitation is presented [6]. The requirements for interface stability are explained in terms of solute solubility at the nanoparticle/water interface and its dependence on both temperature and solvent concentration. The dependence of stability on particle size was also observed on itraconazole and odanacatib NPs. Odanacatib, even with higher bulk solubility than itraconazole, has a longer time scale for ripening due to the larger sized particles and was verified experimentally [6].

The theory of Ostwald ripening provides the framework for understanding the differences in stability observed for the two compounds. The dynamics of the hydrophobic polymer block plays a major role in long term stability as demonstrated by the behavior of nanoparticles stabilized by Poloxamer vs. polystyrene-b-polyethylene oxide polymers[6]. The instability of NP with Poloxamer arises due to the enhanced drug solubility in Poloxamer at the interface and subsequent adsorption and desorption of Poloxamer micelles at the NP surface [6,7].

1. Allen, C.; Maysinger, D.; Eisenberg, A. Colloids and Surfaces B: Biointerfaces, 1999. 16(1-4):p.3.

2. Kumar, V.; Prud'homme, RK. Journal of Pharmaceutical Sciences, 2008. 97:4904-4914.

3. Johnson, BK.; Prud'homme, RK.Physical Review Letter, 2003. 91:118302.

4. Mullin, JW. Crystallization. 1993.

5. Liu, Y.; Saad, W.; Prud'homme, RK. Physical Review Letter, 2007. 98:036102.

6. Kumar, V.; Wang, L.; Riebe, M.; Tung, HH.; Prud'homme, RK. Molecular Pharmaceutics, 2009. In press.

7. Crisp, MT.; Tucker, CJ.; Rogers, TL.; Williams, RO.; Johnston, KP. Journal of Controlled Release, 2007. 117:351-359.