455766 Engineering the Mechanical Properties of Amorphous Solid Dispersion Particles

Wednesday, November 16, 2016: 4:40 PM
Cyril Magnin I (Parc 55 San Francisco)
Alyssa Ekdahl and Aaron Goodwin, Bend Research Inc, a division of Capsugel, Bend, OR

Spray-dried amorphous solid dispersions (SDDs) is one of the most robust and mature available technologies to improve oral absorption of drug candidates with low bioavailability due to poor aqueous solubility and dissolution rate. As an active intermediate of the drug substance, SDDs are readily integrated into oral solid dosage forms, the most common being tablets. However, due to the dilution of the active ingredient in the SDD and then further dilution in the tablet formulation, pill burden can become a problem for less potent drugs. One possible solution is to engineer improved SDD particle mechanical properties through the spray drying process thereby reducing the amount of tablet fillers and improving the robustness of the tableting process. This concept of SDD particle property optimization is a multifaceted optimization problem between physical state and chemical stability of the drug, downstream processing of the resulting powder, and in vivo performance. Although this talk focuses on one aspect of downstream processing, the mechanical properties specifically related to tableting, there have been several recent reviews on this subject [1-2]. The current pharmaceutical literature is rich with information on engineering SDD particles, but there lacks the connection to how these engineering principles influence the compression-related mechanical properties.


The aim of the current study is to make that connection by engineering the mechanical properties of SDD particles through the spray-drying process. Ketoconazole spray-dried with HPMCAS-M or PVP VA-64 at varying concentrations was used as a model SDD system.  Atomization and drying kinetics were adjusted to vary surface area by altering particle size distribution, particle density, and morphology. The mechanical properties were studied using compression profiles, SEM imaging, and yield pressure determination with a modified in-die compression analysis [3]. The results showed that the compression pressures required to reach a 2.0MPa tensile strength compact varied with SDD composition and were in the range of typical fillers. Yield pressures also varied with drug loading and polymer selection which could be reasonably predicted by the pure material behaviors composing the SDD particles. The deformation and tensile strength mechanisms were further evidenced by the SEM micrographs. The results suggest that a tablet formulation using rationally engineered particles could reduce the amount of fillers needed to decrease pill burden.



[1] Patel, B.B. et al. Revealing facts behind spray dried solid dispersion technology used for solubility enhancement.

Saudi Pharm. J. 2015, 23 (4), 352-365.

[2] Singh, A. and Van den Mooter, G. Spray drying formulation of amorphous solid dispersions. Adv. Drug Deliv.

Rev. 2015.

[3] Katz, J. M., Roopwani, R., Buckner, I. S. A Material-Sparing Method for Assessment of Powder Deformation

Characteristics Using Data Collected During a Single Compression-Decompression Cycle. J. Pharm. Sci.

2013, 102 (10), 3687-3693.

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See more of this Session: Engineered and Amorphous Particle Formation Technologies
See more of this Group/Topical: Separations Division