Nano-extrusion: a One-Step Process for Manufacturing of Solid Nanoparticle Formulations Directly from the Liquid Phase

This paper presents a novel one-step process for converting a liquid stabilized nano-suspension into a solid formulation via hot-melt extrusion combined with an internal devolatilization process (nano-extrusion, NANEX). A polymer (Soluplus®) was fed into the extruder and molten, after which a stable nano-suspension was added via side-feeding devices. The solvent (water) was removed by devolatilization and the polymer solidified at the outlet. The solid material can be tableted or filled in a capsule directly. The results showed that the obtained extrudates comprised nanocrystals in the de-aggregated form, confirming that a solid nano-formulation was prepared. This method is capable of overcoming many of the problems associated with other processes involving solid nano-dosage forms and poses a straightforward approach towards manufacturing such products.

[1]  G. Liversidge,et al.  The surface modified drug nanoparticles , 1992 .

[2]  K. Johnston,et al.  Enhanced drug dissolution using evaporative precipitation into aqueous solution. , 2002, International journal of pharmaceutics.

[3]  O. Kayser,et al.  for Poorly Soluble and Poorly Bioavailable Drugs , 2003 .

[4]  Elaine Merisko-Liversidge,et al.  Nanosizing: a formulation approach for poorly-water-soluble compounds. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  S. Walker,et al.  Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964-1985). , 1988, British journal of clinical pharmacology.

[6]  Christopher T. Walsh,et al.  Drugs as materials: valuing physical form in drug discovery , 2004, Nature Reviews Drug Discovery.

[7]  J E Kipp,et al.  The role of solid nanoparticle technology in the parenteral delivery of poorly water-soluble drugs. , 2004, International journal of pharmaceutics.

[8]  Rainer H. Müller,et al.  Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique , 1998 .

[9]  R. Müller,et al.  Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. , 2001, Advanced drug delivery reviews.

[10]  Jouni Hirvonen,et al.  Pharmaceutical nanocrystals by nanomilling: critical process parameters, particle fracturing and stabilization methods , 2010, The Journal of pharmacy and pharmacology.

[11]  Donald L. Wise,et al.  Handbook of Pharmaceutical Controlled Release Technology , 2000 .

[12]  A. Fasano,et al.  Innovative strategies for the oral delivery of drugs and peptides. , 1998, Trends in biotechnology.

[13]  K. Johnston,et al.  Preparation of cyclosporine A nanoparticles by evaporative precipitation into aqueous solution. , 2002, International journal of pharmaceutics.

[14]  Eva Roblegg,et al.  Development of sustained-release lipophilic calcium stearate pellets via hot melt extrusion. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[15]  R. Müller,et al.  Production and characterisation of highly concentrated nanosuspensions by high pressure homogenisation. , 2001, International journal of pharmaceutics.

[16]  Jiraporn Chingunpituk Nanosuspension Technology for Drug Delivery , 2011 .

[17]  Patrick Augustijns,et al.  Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products. , 2008, International journal of pharmaceutics.

[18]  G. Liversidge,et al.  Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats , 1995 .

[19]  R. Davé,et al.  Recovery of BCS Class II drugs during aqueous redispersion of core–shell type nanocomposite particles produced via fluidized bed coating , 2013 .

[20]  Kenneth A Dawson,et al.  A new methodology for studying nanoparticle interactions in biological systems: dispersing titania in biocompatible media using chemical stabilisers. , 2011, Nanoscale.