Effect of Particle Size of Powdered Cellulose Nanofibers as an Additive in the Production of Orally Disintegrating Mini-Tablets by Direct Powder Compression.

Abstract

Mini-tablets (MTs) allow for dosage adjustments according to children's weight and age. However, it is difficult to manufacture MTs with robust physical properties, and various formulation techniques are required. Adding cellulose nanofiber (CNF), a highly functional biomass material, to MTs improved the hardness and disintegration; however, the large variation in the weight and drug content of the resulting MTs remained a challenge. Therefore, this study analyzed the physical properties of CNF-containing MTs of different particle sizes and evaluated the effect of the particle size on MT manufacturing. CNF₃₀₀, with an average particle size of approximately 300 µm, was pulverized to prepare CNF₁₀₀, averaging 100 µm. The formulation included CNF (10, 30, and 50%), lactose hydrate, paracetamol, and magnesium stearate. The pharmaceutical powders mixed were loaded into a rotary tablet press equipped with a 3-mm multiple-tip tooling and compressed at 2, 5, and 8 kN forces. CNF₁₀₀-containing MTs were manufactured via direct powder compression, and they showed lower variations in weight and drug content than those containing CNF₃₀₀. The tensile strength of MTs containing CNF₁₀₀ was smaller than that of those containing CNF₃₀₀; however, a strength of ≥1 MPa (corresponding to ≥30 N hardness of a regular tablet) was obtained by setting the compression force to ≥5 kN. The MTs containing 30% CNF₁₀₀ disintegrated in ≤30 s, regardless of the compression force. Thus, using smaller CNF particle sizes enabled the manufacturing of an orally disintegrating MT with adequate hardness and disintegration properties while also minimizing variations in MT weight and drug content.