(350v) Can You Improve Dissolution Rate of Micronized Poorly Water-Soluble Drugs after Dry Coating with Hydrophobic Silica?

Dry coating of silica has been shown to be very helpful with enhancing flow and bulk density of all types of powders¹. However, its effect on the dissolution of poorly water-soluble drugs has not been well-understood, most reports have dealt with a coating of hydrophilic silicas^2,3. A major challenge with fine powders, in particular those below 30μm, is significant agglomeration due to high cohesion that delays their dissolution rate². 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. It is possible that if the agglomerate sizes are reduced greatly, even the use of hydrophobic silica could promote their dissolution rate after coating due to the increased surface area that gets exposed to the dissolution medium. However, the previous reports have not quantified agglomerate size reduction after dry coating, along with its competing relationship with the surface hydrophobicity on the drug dissolution rate^3,4. 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, which were dry coated with either hydrophilic (A200) or hydrophobic (R972P) fumed silica via LabRAM at 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^5,6. 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 work⁷. The applicability of the previously presented mathematical correlation between a bond number to an agglomerate ratio⁸ 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. The outcomes from this study help answer the original question about if and when even hydrophobic silica coating can help improve the dissolution rate of poorly water-soluble drug through the understanding of the impacts of the surface hydrophobicity and the agglomerate size.

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. Washburn, E. W., The dynamics of capillary flow. Physical Review 1921, 17 (3), 273-283.
6. 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).
7. Chen, Y.; Yang, J.; Dave, R. N.; Pfeffer, R., Fluidization of coated group C powders. AIChE Journal 2008, 54 (1), 104-121.
8. 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.