The effects of spray drying, HPMCAS grade, and compression speed on the compaction properties of itraconazole-HPMCAS spray dried dispersions

Moshe Honick; Sharmila Das; Stephen W Hoag; Francis X Muller; Alaadin Alayoubi; Xin Feng; Ahmed Zidan; Muhammad Ashraf; James E Polli

doi:10.1016/j.ejps.2020.105556

The effects of spray drying, HPMCAS grade, and compression speed on the compaction properties of itraconazole-HPMCAS spray dried dispersions

Eur J Pharm Sci. 2020 Dec 1:155:105556. doi: 10.1016/j.ejps.2020.105556. Epub 2020 Sep 16.

Authors

Moshe Honick¹, Sharmila Das¹, Stephen W Hoag¹, Francis X Muller², Alaadin Alayoubi³, Xin Feng³, Ahmed Zidan³, Muhammad Ashraf³, James E Polli⁴

Affiliations

¹ University of Maryland, Department of Pharmaceutical Sciences, 20 Penn Street, Baltimore, MD 21201, USA.
² Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE 19803 USA.
³ Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, White Oak, MD 20993, USA.
⁴ University of Maryland, Department of Pharmaceutical Sciences, 20 Penn Street, Baltimore, MD 21201, USA. Electronic address: jpolli@rx.umaryland.edu.

PMID: 32946956
DOI: 10.1016/j.ejps.2020.105556

Abstract

Spray dried dispersions (SDDs) have the potential to dramatically improve the oral bioavailability of drugs with poor water solubility. However, SDDs tend to have material attributes, such as small particle size, low bulk density, and poor flowability, which are undesirable for downstream processing such as tableting. The objective was to perform a comprehensive compaction characterization of both physical mixtures and SDDs consisting of itraconazole (ITZ) and hypromellose acetate succinate (HPMCAS) to elucidate process and material influences on compressibility and compactibility. We fabricated SDDs with 20% ITZ as a model BCS Class 2 drug and 80% HPMCAS as a polymer carrier. Results indicate that SDDs, as well physical mixtures of ITZ and HPMCAS, were easily deformable with similar compressibility profiles across all compression speeds. Analysis of Heckel plots revealed that yield pressures were fairly low for both physical mixtures and SDDs (43.97-59.75 MPa), indicative of ductile materials. SDDs had a much greater propensity to laminate, especially at higher compression speeds, compared to physical mixtures. This difference is likely due to the higher elastic recovery of SDDs. However, for intact tablets, the mechanical strength of compacts from SDDs tended to be higher than those produced from physical mixtures, likely due to the much smaller particle size of the SDDs. Importantly, examination of the compacts with differential scanning calorimetry did not detect any drug crystallization as a result of compaction. In conclusion, while spray drying did not significantly alter the compressibility of binary mixtures ITZ and HPMCAS, it dramatically impacted compactibility and tabletability, increasing elastic recovery, and making the mixtures more prone to lamination. However, at low compression speeds, SDDs produced tablets with higher tensile strength than physical mixtures.

Keywords: Compaction; Hypromellose acetate succinate; Itraconazole; Lamination; Spray dried dispersion.

MeSH terms

Drug Compounding
Itraconazole*
Methylcellulose*
Solubility
Spray Drying
Tablets

Substances

Tablets
Itraconazole
Methylcellulose