Tablets having wide ranges of dosages are the preferred form of solid dosage form
1,2. However, for pediatric or highly potent tablets, the major challenge is to achieve uniformity of active pharmaceutical ingredients (API)
1,3. For that purpose, the APIs are often micronized to improve the drug content uniformity, where micronization is also expected to promote faster dissolution and subsequent absorption
3,4. However, once the powders are micronized, their cohesiveness increases
5,6 forming agglomerates and thus adversely impacting the content uniformity of the powder blends, not to mention, often requiring wet granulation
3. The recent study by Huang et al. 2017 demonstrated that the dry coating technique could alleviate the problem while avoiding wet granulation since it can significantly decrease interparticle cohesion
7, hence mitigating the adverse impacts from typical large agglomerates
3. Although that work demonstrated the benefit of the dry coating technique, the model API was not poorly water-soluble, and the formulation consisted of a drug-excipient binary mixture. However, most tablet formulations consist of multi-component excipient powders and increasingly involve poorly water-soluble APIs. Therefore, the current work addresses that gap by investigating the effect of dry coated poorly water-soluble API (ibuprofen,
d50 of 10 to 13 microns) within the multi-component tablet blends having 4 additional components that are different types of excipients: lactose monohydrate, a filler, micro cellulose crystalline, a tablet binder and a filler, crospovidone, a disintegrant, and magnesium stearate, a lubricant during tableting operations. For eliminating the confounding effect from size driven segregation
8 during mixing, all these components were selected to be in similar size ranges as the API
4; i.e., crospovidone, magnesium stearate, lactose monohydrate, micro cellulose crystalline have mean particle size (
d50) of 38μm, 8μm, 19μm, and 20 μm, respectively. The changes in the bulk powder properties (flowability, bulk, and true densities) and tablet properties (API release rate, and tensile strength) were also measured and analyzed. In addition, the use of two different types of silica for dry coating were considered, following a recent work (Kim et al. 2021
9), which demonstrated complex combined effect from agglomerate size reduction and surface wettability, both induced by the silica type, amount, and coating effectiveness. The experimental results demonstrated that even with a 5-components powder blend system, the dry coating of the micronized and cohesive poorly water-soluble API significantly improved the content uniformity of API at each of three, 1, 3, and 5%, drug loadings. Considering there are rather low drug loadings, improvements in powder flowability or bulk densities after dry coating were minimal as was expected. Interestingly, there were noticeable changes in the tablet tensile strength and API release rates when the tablets contain dry coated API. The relationship between the surface energy of the dry coated API and the API release rate from the multi-component tablets was also examined.
References
1. Lopez, F. L.; Ernest, T. B.; Tuleu, C.; Gul, M. O., Formulation approaches to pediatric oral drug delivery: Benefits and limitations of current platforms. Expert Opinion on Drug Delivery 2015, 12 (11), 1727-1740.
2. Bhutani, U.; Basu, T.; Majumdar, S., Oral Drug Delivery: Conventional to Long Acting New-Age Designs. European Journal of Pharmaceutics and Biopharmaceutics 2021, 162, 23-42.
3. 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.
4. 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.
5. Nase, S. T.; Vargas, W. L.; Abatan, A. A.; McCarthy, J. J., Discrete characterization tools for cohesive granular material. Powder Technology 2001, 116 (2-3), 214-223.
6. Castellanos, A.; Valverde, J. M.; Quintanilla, M. A. S., Fine cohesive powders in rotating drums: Transition from rigid-plastic flow to gas-fluidized regime. Physical Review E - Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics 2002, 65 (6).
7. Chen, Y.; Yang, J.; Dave, R. N.; Pfeffer, R., Fluidization of coated group C powders. AIChE Journal 2008, 54 (1), 104-121.
8. Figueroa, I.; McCarthy, J. J., Using janus particles to control mixing and segregation of adhesive particle systems. Industrial and Engineering Chemistry Research 2010, 49 (11), 5204-5214.
9. Kim, S.; Biligili, E.; Dave, R. N., Impact of hydrophobicity of dry coating material on the dissolution of micronized BCS class II drug powders. Submitted to Interntional Journal of Pharmaceutics 2021.
