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Downstream Processing of Itraconazole:HPMCAS Amorphous Solid Dispersion: From Hot-Melt Extrudate to Tablet Using a
Saurabh M Mishra1, Margarethe Richter2, Luis Mejia1
1SE Tylose USA Inc., Pharmaceutical Application Laboratory, Totowa, NJ 07512, USA.
Pharmaceutics
|July 27, 2022
Summary
Processing amorphous solid dispersions (ASDs) into tablets is challenging. Chill roll flaking improved ASD yield, particle size, tabletability, and dissolution compared to other sizing methods.
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Materials Science
Background:
- Hot-melt extrusion (HME) is used to create amorphous solid dispersions (ASDs) for improved drug solubility.
- Downstream processing of HME ASDs into tablets faces challenges due to poor tabletability of milled extrudates.
- Strand sizing before milling is necessary but can influence critical quality attributes (CQAs).
Purpose of the Study:
- To systematically investigate the impact of different strand sizing technologies on the milling and tableting of an itraconazole-HPMCAS ASD.
- To evaluate how milling parameters (speed, screen size) and sizing methods affect ASD CQAs.
- To determine the relationship between particle size distribution (PSD) and tablet performance.
Main Methods:
- An amorphous solid dispersion of itraconazole with hypromellose acetate succinate (HPMCAS) was prepared via hot-melt extrusion.
- Extruded strands were sized using hand-cutting, pelletizer, or chill roll and flaker systems.
- Sized materials were milled under various conditions (speed, screen size), and CQAs (yield, D50, tabletability, dissolution) were analyzed using response surface methodology.
Main Results:
- Sizing technology significantly impacted ASD CQAs; chill roll flakes yielded the highest percentage yield and lowest mean particle size (D50).
- Chill roll flaking resulted in superior tabletability and dissolution rates for itraconazole ASDs.
- Pearson correlation indicated D50 as the most critical CQA influencing tabletability and dissolution.
Conclusions:
- Chill roll and flaker systems are advantageous for sizing HME ASD extrudates, enhancing yield, particle characteristics, and drug product performance.
- Optimizing milling conditions can achieve comparable particle size distributions across different sizing methods.
- Controlling particle size (D50) is crucial for successful downstream processing and achieving desired tablet properties for ASDs.
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