Downstream processing of spray-dried ASD with hypromellose acetate succinate - Roller compaction and subsequent compression into high ASD load tablets

Andreas Sauer; Shogo Warashina; Saurabh M Mishra; Ilja Lesser; Katja Kirchhöfer

doi:10.1016/j.ijpx.2021.100099

Downstream processing of spray-dried ASD with hypromellose acetate succinate - Roller compaction and subsequent compression into high ASD load tablets

Int J Pharm X. 2021 Oct 14:3:100099. doi: 10.1016/j.ijpx.2021.100099. eCollection 2021 Dec.

Authors

Andreas Sauer¹, Shogo Warashina², Saurabh M Mishra³, Ilja Lesser¹, Katja Kirchhöfer¹

Affiliations

¹ SE Tylose GmbH & Co. KG, Kasteler Str. 45, 65203 Wiesbaden, Germany.
² Shin-Etsu Chemical Co. Ltd, 28-1 Nishifukushima, Kubiki-ku, Joetsu-shi, Niigata, Japan.
³ SE Tylose USA Inc, Pharmaceutical Application Laboratory, Totowa, NJ 07512, USA.

Abstract

Despite wide commercial application of hypromellose acetate succinate (HPMCAS) in spray-dried amorphous solid dispersion (ASD) drug products, little information is available in the references on downstream processing of spray-dried dispersions with HPMCAS. Poor flow and high dilution factor are a challenge in formulating spray-dried ASDs into tablets, leaving little space for other excipients facilitating binding and disintegration. Direct compression is not possible due to the poor powder flow of spray-dried ASDs. Moisture has to be avoided due to the plasticizing properties of water on the ASD, resulting in reduced stability of the amorphous state. Thus, dry granulation by roller compaction and subsequent tablet compression is the preferred downstream process. We report the investigation of downstream processing by roller compaction and tablet compression of a high load formulation with 75% of spray-dried amorphous solid dispersion (Nifedipine:HPMCAS 1:2). A head to head comparison of microcrystalline cellulose/croscarmellose (MCC/cl-NaCMC) as binder/disintegrant vs. MCC and low-substituted hydroxypropyl cellulose (L-HPC) as excipient for binding and disintegration showed improved re-workability of the formulation with MCC/L-HPC after roller compaction. Upon transfer to the rotary press, a 45% higher tensile strength of tablets is observed after dry granulation with MCC/L-HPC.

Keywords: Amorphous solid dispersion; Downstream processing; Dry granulation; Hypromellose acetate succinate; Low-substituted hydroxypropyl cellulose; Spray drying.