A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets

Deanna M Mudie; Stephanie Buchanan; Aaron M Stewart; Adam Smith; Kimberly B Shepard; Nishant Biswas; Derrick Marshall; Alyssa Ekdahl; Amanda Pluntze; Christopher D Craig; Michael M Morgen; John M Baumann; David T Vodak

doi:10.1016/j.ijpx.2020.100042

A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets

Int J Pharm X. 2020 Feb 19:2:100042. doi: 10.1016/j.ijpx.2020.100042. eCollection 2020 Dec.

Authors

Affiliations

¹ Global Research and Development, Lonza, Bend, Oregon 97703, USA.
² Daniel Felix Ritchie School of Engineering & Computer Science, University of Denver, Denver, CO 80210, USA.
³ Pivotal Drug Product Technologies, Amgen, Cambridge, MA 02141, USA.
⁴ Cockrell School of Engineering, The University of Texas at Austin, Austin, TX 78712, USA.

Abstract

Although Amorphous Solid Dispersions (ASDs) effectively increase bioavailability, tablet mass can be high due to the large fraction of excipients needed to stabilize the amorphous drug in the solid state, extend drug supersaturation in solution and achieve robust manufacturability. The aim of this work was to reduce tablet mass of an ASD tablet comprising a low glass transition temperature (T_g), rapidly crystallizing drug without compromising these key attributes. In this approach, erlotinib (T_g = 42 °C, T_m/T_g = 1.4 K/K) was spray dried with the high T_g polymer poly(methyl methacrylate-co-methacrylic acid) (Eudragit® L100, Evonik) (T_g = 187 °C) to facilitate high drug loading while maintaining physical stability. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) (AQOAT® HF, Shin-Etsu) was granulated with the ASD to extend supersaturation in solution. For comparison, a benchmark ASD was spray dried at a lower drug loading with HPMCAS-H (T_g = 119 °C). This High Loaded Dosage Form (HLDF) approach reduced tablet mass by 40%, demonstrated similar physical stability and in vitro performance as the benchmark and exhibited excellent downstream manufacturability. Strategically combining two different polymers in a tablet to maintain physical stability and sustain supersaturation in solution can decrease tablet mass of some low T_g, rapidly crystallizing amorphous drugs.

Keywords: Amorphous solid dispersion; Bioavailability enhancement; Concentration sustainment; Eudragit L100; Physical stability; Solid dosage form; Spray drying.