Slavomira Doktorovova ^a, Elaine H. Stone ^b, João Henriques ^a. 

^a Drug Produt Development, R&D, Hovione FarmaCiencia SA Lisbon, Portugal 
^b Merlin Powder Characterisation Ltd, Brierley Hill, United Kingdom 

Purpose. Amorphous solid dispersions (ASD) are a proven method of improving the solubility and bioavailability of poorly soluble compounds. It is important that the resulting ASD has suitable properties for tableting, especially if high does are required. The purpose of this study was to examine spray dried ASD sensitivity to strain rate under compression. Amorphous solid dispersions consist of API and a stabilizing polymer. Polymers tend to show plastic deformation behavior, typically prone to yield pressure sensitivity to compression speed. Furthermore, we also investigated the drivers for such a strain sensitive behavior.  

Methods. A set of sample spray dried powders, selected for their range of properties, was compressed using a simulated Korsch XL100 profile and ~200 mS and ~ 20 mS dwell time on a Phoenix compaction simulator. The sample set included samples with varying API content (0 – 50% w/w), stabilizing polymer (HPMC, HPMC-AS, PVP-VA), particle size and bulk densities (BD), produced on spray driers from lab scale to commercial scale. Strain rate sensitivity was evaluated based on yield pressure differences normalized to yield pressure at slow speed and tensile strength (TS) difference at compression pressure ~100 MPa normalized to TS at slow speed. 

Results. Yield pressure differences varied from practically absent to ~ 20%. TS difference varied from ~5% to ~45% and was more pronounced with increasing API load and decreasing bulk density. Additionally, decreasing particle size and increasing residual solvent content was seen to contribute to increased TS differences.  

Conclusions. Spray dried material properties leading to compression speed sensitivity were identified. These observations can aid in the formulation of spray dried ASDs in order to minimize the impact in downstream process development and scale-up. 

Biosketch: Slavomíra Doktorovová

Slavomíra Doktorovová is a Pharmacist by training. She holds a Master degree in Pharmacy, received from Comenius University in Bratislava, Slovakia and PhD in genetics from University of Trás-os-montes e Alto Douro (IBB-CGB/UTAD) in Vila Real, Portugal. Slavomira joined Hovione´s Drug Product Development department in 2016, where she is technical lead for multiple drug product development projects. Since joining Hovione, she has supported formulation and process development of multiple tableting, roller compaction, capsule filling, micronization and spray drying projects.