The effects of spray drying, HPMCAS grade, and compression speed on the compaction properties of itraconazole-HPMCAS spray dried dispersions
Sept. 16, 2020, midnight
Stephen W. Hoag
Francis X. Muller
James E. Polli
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Spray-dried dispersions (SDDs) hold considerable potential in enhancing the oral bioavailability of drugs with limited water solubility. Nevertheless, SDDs often exhibit material attributes, such as small particle size, low bulk density, and suboptimal flowability, which are undesirable for subsequent processing steps like tableting. This study aimed to comprehensively characterize the compaction behavior of both physical mixtures and SDDs comprising itraconazole (ITZ) and hypromellose acetate succinate (HPMCAS), shedding light on the influences of process and material on compressibility and compactibility.
SDDs were formulated with 20% ITZ (a model BCS Class 2 drug) and 80% HPMCAS as a polymer carrier. The results indicated that SDDs, along with physical mixtures of ITZ and HPMCAS, exhibited similar compressibility profiles at various compression speeds, showcasing ease of deformability. Heckel plot analysis suggested low yield pressures for both physical mixtures and SDDs (43.97-59.75 MPa), indicative of ductile materials. Notably, SDDs showed a higher tendency to laminate, particularly at elevated compression speeds, attributed to their higher elastic recovery. However, intact tablets from SDDs demonstrated greater mechanical strength compared to those from physical mixtures, likely due to the significantly smaller particle size of the SDDs.
Crucially, differential scanning calorimetry examination of the compacts did not reveal any drug crystallization resulting from compaction. In conclusion, while spray drying did not significantly alter the compressibility of binary mixtures of ITZ and HPMCAS, it distinctly impacted compactibility and tabletability, increasing elastic recovery and making the mixtures more susceptible to lamination. However, at low compression speeds, SDDs produced tablets with higher tensile strength than physical mixtures.