(643a) Evaluating the Performance of Hydrophobic Versus Hydrophilic Silica Coating of API Powders on Their Critical Properties As Well As of Their Blends

Sangah Kim, Rajesh Dave^* (corresponding author at: dave@njit.edu)

Particle cohesion relative to particle weight increases with powder size reduction requiring powder engineering to reduce interparticle cohesiveness, thus improving powder flowability, compressibility, and dispersibility ^1-9. The solventless mechanical dry coating, done through various methods including a high-intensity vibratory coater ^{6, 10, 11}, is an exemplary powder engineering method to decreasing interparticle cohesion. Various nanoparticles have been examined as surface coating materials. Amongst many dry coating approached, the one based on using a high-intensity vibratory coater (high-intensity acoustic mixer) has been reported to be the most effective dry coating approach ^12-14 in combination with nano-fumed silica (colloidal silica). Several studies have reported considerable bulk powder properties enhancements, including flowability, bulk density, compaction behavior, agglomerate reduction, and dissolution for cohesive host powders dry coated with colloidal silica ^15-20. To date, such reports did not examine the impact of the inherent physicochemical properties of host particles for selecting colloidal silica except for the inverse relationship between the host particle size and the amount of colloidal silica required to achieve the targeted SAC. The properties such as total surface energy (dispersive energy and polarity), log P value, and morphology (shape and surface texture) are also expected to influence the selection of the adequate amount and type of colloidal silica for achieving the desired bulk properties enhancement and have not been examined in detail.

Therefore, this work examines the effectiveness of different types and the amounts of silicas in improving the bulk properties of various host powders with differing physical and chemical properties. The dry coating formulation considered fixed surface area of the host particle covered by guest particles with constant %SAC instead of a fixed weight percent of silica. The degree of powder properties enhancement at a fixed %SAC were also considered to avoid adding excessive silica to account for the differing sizes of the silicas used. Consequently, a fair comparison of the degree of bulk properties enhancement for single and blended powders at the same dry coating quality with different silica was assured.

Four different colloidal silica, three hydrophilic silica of different sizes (M5P, A200, A300) and one hydrophobic silica (R972P) were selected as the guests. Four cohesive active pharmaceutical ingredients (APIs), micronized acetaminophen, micronized ibuprofen, micronized fenofibrate, and griseofulvin, all similar-sized having d₅₀ of 10-15 µm, but physiochemically different were chosen as the hosts. The guest-host pairs were tested to determine which guest powder was the most effective to improve the host powder's properties by studying flowability, bulk density, and agglomeration at the same %SAC. One of the APIs, micronized acetaminophen, was selected as the key model host powder for preparing blends with fine excipients. Four different blends were considered, one each with mAPAP dry coated with one of four selected silicas. The bulk properties, e.g., flowability, bulk density, agglomeration, and API release rate, of the four types of blends were evaluated to determine the best performing silica type. Overall, this study allowed for examining the impact of silica type on the individual API’s bulk property enhancements but also examine such properties of their blends since the mixing of dry coated APIs could also lead to synergistic enhancements due to preferential silica transfer to the excipients.

All dry coated APIs showed good bulk properties (FFC, BD, and AR) enhancement, with no disparate results as %SAC and silica differed, as per Chen’s multi-asperity model predicted ²¹. Nonetheless, when the most cohesive API (mAPAP) was tested for its blend properties, R972P with 50% SAC dry coating was the most effective dry coating formulation, enabling the DB-DC process without negatively affecting tablet tensile strength and API release rate. The intricate impacts from guest-host size ratio, host %SAC, the affinity between silica to API/excipients, and finally mixing effect, R972P 50% SAC was the most effective dry coating formulation which satisfied tested several key product quality attributes (FFC, BD, AR, tablet strength, and API release rate). Much improved blend flowability and API cohesion reduction, as shown in the agglomerate analysis, good uniformity and low tablet-to-tablet weight variability are expected ²². Overall, the compiled analysis suggests eliminating the need for additional processing steps (a.k.a. wet/dry granulation) and expanding excipient selection pools.

References

(1) Pfeffer, R.; Dave, R. N.; Wei, D.; Ramlakhan, M. Synthesis of engineered particulates with tailored properties using dry particle coating. Powder Technology 2001, 117 (1-2), 40-67. DOI: 10.1016/S0032-5910(01)00314-X Scopus.

(2) Espin, M. J.; Ebri, J. M. P.; Valverde, J. M. Tensile strength and compressibility of fine CaCO3 powders. Effect of nanosilica addition. Chemical Engineering Journal 2019, 378, Article. DOI: 10.1016/j.cej.2019.122166 Scopus.

(3) Koishi, M.; Honda, H.; Ishizaka, T.; Matsuno, T.; Katano, T.; Ono, K. Surface Modification of powders by the high speed impact treatment method. Journal of the Society of Powder Technology Japan 1987, 5 (78).

(4) Ouabbas, Y.; Chamayou, A.; Galet, L.; Baron, M.; Thomas, G.; Grosseau, P.; Guilhot, B. Surface modification of silica particles by dry coating: Characterization and powder ageing. Powder Technology 2009, 190 (1-2), 200-209, Article. DOI: 10.1016/j.powtec.2008.04.092 Scopus.

(5) Mullarney, M. P.; Beach, L. E.; Davé, R. N.; Langdon, B. A.; Polizzi, M.; Blackwood, D. O. Applying dry powder coatings to pharmaceutical powders using a comil for improving powder flow and bulk density. Powder Technology 2011a, 212 (3), 397-402. DOI: 10.1016/j.powtec.2011.06.008 Scopus.

(6) Mullarney, M. P.; Beach, L. E.; Langdon, B. A.; Polizzi, M. A. Applying dry powder coatings: Using a resonant acoustic mixer to improve powder flow and bulk density. Pharmaceutical Technology 2011b, 35 (10), 94-102, Article. Scopus.

(7) Naito, M.; Hotta, T.; Fukui, T. Applications of Comminution Techniques for the Surface Design of Powder Materials. Key Engineering Materials 2003, 253, 275-292. Scopus.

(8) Yokoyama, T.; Urayama, K.; Naito, M.; Kato, M.; Yokoyama, T. The Angmill Mechanofusion System and its Applications. KONA Powder and Particle Journal 1987, 5, 59-68. DOI: 10.14356/kona.1987011 Scopus.

(9) Xie, H. Y. The role of interparticle forces in the fluidization of fine particles. Powder Technology 1997, 94 (2), 99-108. DOI: 10.1016/S0032-5910(97)03270-1.

(10) Kottlan, A.; Glasser, B. J.; Khinast, J. G. Powder bed dynamics of a single-tablet-scale vibratory mixing process. Powder Technology 2023, 414, Article. DOI: 10.1016/j.powtec.2022.118029 Scopus.

(11) Osorio, J. G.; Muzzio, F. J. Evaluation of resonant acoustic mixing performance. Powder Technology 2015, 278, 46-56, Article. DOI: 10.1016/j.powtec.2015.02.033 Scopus.

(12) Dave, R. N.; S. Kim; K. Kunnath; Tripathi, S. A concise treatise on model-based enhancements of cohesive powder properties via dry particle coating. Advanced Powder Technology 2022, 33 (103836).

(13) 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 2018a, 536 (1), 127-137. DOI: 10.1016/j.ijpharm.2017.11.060 Scopus.

(14) Capece, M.; Huang, Z.; Davé, R. Insight Into a Novel Strategy for the Design of Tablet Formulations Intended for Direct Compression. Journal of Pharmaceutical Sciences 2017, 106 (6), 1608-1617, Article. DOI: 10.1016/j.xphs.2017.02.033 Scopus.

(15) Kojima, T.; Elliott, J. A. Effect of silica nanoparticles on the bulk flow properties of fine cohesive powders. Chemical Engineering Science 2013, 101, 315-328, Article. DOI: 10.1016/j.ces.2013.06.056 Scopus.

(16) Sunkara, D.; Capece, M. Influence of Material Properties on the Effectiveness of Glidants Used to Improve the Flowability of Cohesive Pharmaceutical Powders. AAPS PharmSciTech 2018, 19 (4), 1920-1930, Article. DOI: 10.1208/s12249-018-1006-3 Scopus.

(17) 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. DOI: 10.1016/j.ijpharm.2018.04.002 Scopus.

(18) Jallo, L. J.; Dave, R. N. Explaining Electrostatic Charging and Flow of Surface-Modified Acetaminophen Powders as a Function of Relative Humidity Through Surface Energetics. Journal of Pharmaceutical Sciences 2015, 104 (7), 2225-2232. DOI: 10.1002/jps.24479 Scopus.

(19) Kim, S.; Bilgili, E.; Davé, R. N. Impact of altered hydrophobicity and reduced agglomeration on dissolution of micronized poorly water-soluble drug powders after dry coating. International Journal of Pharmaceutics 2021, 606, Article. DOI: 10.1016/j.ijpharm.2021.120853 Scopus.

(20) Cares Pacheco, M. G.; Jiménez Garavito, M. C.; Ober, A.; Gerardin, F.; Silvente, E.; Falk, V. Effects of humidity and glidants on the flowability of pharmaceutical excipients. An experimental energetical approach during granular compaction. International Journal of Pharmaceutics 2021, 604, Article. DOI: 10.1016/j.ijpharm.2021.120747 Scopus.

(21) Chen, Y.; Yang, J.; Dave, R. N.; Pfeffer, R. Fluidization of coated group C powders. AIChE Journal 2008, 54 (1), 104-121. DOI: 10.1002/aic.11368 Scopus.

(22) Kim, S. S.; Seetahal, A.; Amores, N.; Kossor, C.; Davé, R. N. Impact of dry coating and mixing time on flowability and drug content uniformity of medium drug loaded fine API blends. Journal of Pharmaceutical Sciences 2023b, Under review.