(98a) Impact of Dry Coating on the Agglomeration and Dissolution of Cohesive, Poorly Water-Soluble Drug Powders

For fine powders, in particular those below 30μm, interparticle cohesion is the dominating force, inducing significant agglomerate formation that delays their dissolution rate^1,2. For such fine powders, dry coating with glidants, typically silica nanoparticles, is very effective in reducing cohesion and hence the extent of agglomeration^3,4. Previous papers have reported on the impact of dry coating on enhancements in drug powder bulk density, flow, and dissolution^5,6,7,8,9. However, those papers did not quantify the extent of agglomerate size reduction and its impact on the dissolution^3,4. In addition to presumed agglomerate size reduction after dry coating, the competing relationship with the surface hydrophobicity on the drug dissolution rate was not examined. In this work, the investigation is carried out to fill these gaps and develop a more quantitative understanding of the relationship between cohesion reduction and agglomerate size reduction. The latter objective will be based on proposing a predictive model that is based on the dimensionless parameter that captures the effect of interparticle cohesion, in the form of the granular Bond number. Griseofulvin (d₅₀ of 10 µm) and ibuprofen (d₅₀ of 20 µm) were selected as model drugs. Each drug was dry coated with either hydrophilic (A200) or hydrophobic (R972P) fumed silica via LabRAM, while varying theoretical surface area coverage (SAC) of silica. Agglomerated and primary particle sizes were evaluated by two different particle sizers, a gravity-driven dispersion method, and a compressed air dispersion method, respectively. Following USP <711> protocol, USP IV dissolution testing was conducted in de-ionized water. Surface hydrophilicity was measured via the modified Washburn method^10,11. Inverse gas chromatography was employed to measure the surface energy of the dry coated powders. The results show that the dissolution rate significantly influenced by the changed surface hydrophilicity and the reduced agglomerate size. The multi-asperity model was employed to calculate the bond number for this work¹², utilizing the measured surface energy of the dry coated drug particles. The applicability of the previously presented mathematical correlation between a bond number to an agglomerate ratio¹³ was tested by comparing the predicted agglomerate size to the measured agglomerate size keeping in mind that it does not account for the polydispersity of the powders and process shear effect from the dry coating. Overall, the outcomes from this study will help the design of solid oral dosages through the understanding of the impacts of the surface hydrophobicity and the agglomerate size after dry coating on the dissolution of poorly water-soluble drugs.

References

1. Yang, J.; Sliva, A.; Banerjee, A.; Dave, R. N.; Pfeffer, R., Dry particle coating for improving the flowability of cohesive powders. Powder Technology 2005, 158 (1-3), 21-33.
2. de Villiers, M. M., Influence of agglomeration of cohesive particles on the dissolution behaviour of furosemide powder. International Journal of Pharmaceutics 1996, 136 (1-2), 175-179.
3. Han, X.; Ghoroi, C.; To, D.; Chen, Y.; Davé, R., Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles. International Journal of Pharmaceutics 2011, 415 (1-2), 185-195.
4. Han, X.; Ghoroi, C.; Davé, R., Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading. International Journal of Pharmaceutics 2013, 442 (1-2), 74-85.
5. Jallo, L. J.; Ghoroi, C.; Gurumurthy, L.; Patel, U.; Davé, R. N., Improvement of flow and bulk density of pharmaceutical powders using surface modification. International Journal of Pharmaceutics 2012, 423 (2), 213-225.
6. Huang, Z.; Xiong, W.; Kunnath, K.; Bhaumik, S.; Davé, R. N., Improving blend content uniformity via dry particle coating of micronized drug powders. European Journal of Pharmaceutical Sciences 2017, 104, 344-355.
7. Capece, M.; Huang, Z.; To, D.; Aloia, M.; Muchira, C.; Davé, R. N.; Yu, A. B., Prediction of porosity from particle scale interactions: Surface modification of fine cohesive powders. Powder Technology 2014, 254, 103-113.
8. Chen, L.; Ding, X.; He, Z.; Huang, Z.; Kunnath, K. T.; Zheng, K.; Davé, R. N., Surface engineered excipients: I. improved functional properties of fine grade microcrystalline cellulose. International Journal of Pharmaceutics 2018, 536 (1), 127-137.
9. Kunnath, K.; Huang, Z.; Chen, L.; Zheng, K.; Davé, R., Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating. International Journal of Pharmaceutics 2018, 543 (1-2), 288-299.
10. Thakker, M.; Karde, V.; Shah, D. O.; Shukla, P.; Ghoroi, C., Wettability measurement apparatus for porous material using the modified Washburn method. Measurement Science and Technology 2013, 24 (12).
11. Washburn, E. W., The dynamics of capillary flow. Physical Review 1921, 17 (3), 273-283.
12. Chen, Y.; Yang, J.; Dave, R. N.; Pfeffer, R., Fluidization of coated group C powders. AIChE Journal 2008, 54 (1), 104-121.
13. Castellanos, A., The relationship between attractive interparticle forces and bulk behaviour in dry and uncharged fine powders. Advances in Physics 2005, 54 (4), 263-376.