Effect of Powdered Cellulose Nanofiber with Different Particle Sizes on the Physical Properties of Tablets Manufactured via Direct Compression.

Direct compression is a tableting technique that involves a few steps in non-demanding manufacturing conditions. High strength and rapid disintegration of tablet formulations were previously achieved through the addition of cellulose nanofibers (CNFs), which have recently attracted attention as a high-performance biomass material. However, CNF addition results in greater variation in tablet weight and drug content, potentially due to differences in particle size between CNF and other additives. Herein, we used pulverized CNF to evaluate the effect of CNF particle size on the variation in tablet weight and drug content. Tablet formulations consisted of CNF with different particle sizes (approximately 100 µm [CNF100] and 300 µm [CNF300], at 0, 10, 30, or 50%), lactose hydrate, acetaminophen, and magnesium stearate. Ten powder formulations with different particle sizes and CNF concentrations were prepared; thereafter, the tablets were produced using a rotary tableting press with a compression force of 10 kN. The variation in weight and drug content as well as the tensile strength, friability, disintegration time, and drug dissolution of tablets were evaluated. CNF100 addition to the tablets reduced the weight and drug content variation to a greater extent than CNF300 addition. Using CNF300, we produced tablets of sufficient strength and short disintegration time. These properties were also achieved with CNF100 addition. Our findings suggest that adding CNF of small particle size to the tablet formulation can reduce the variation in weight and drug content while maintaining high strength and short disintegration time.

Effects of Granulated Lactose Characteristics and Lubricant Blending Conditions on Tablet Physical Properties in Direct Powder Compression.

Lactose is an excipient used extensively for bulking, diluting, and molding active pharmaceutical ingredients in tablet manufacturing. Particularly, granulated lactose (GL) intended for direct powder compression has distinct properties due to differences in manufacturing methods. It contributes to handling blended powders for tableting and tablet quality. In this study, we aimed to compare the functions of different forms of GL added as excipients during direct powder compression on the tablet properties and the effect of magnesium stearate (Mg-S) used as a lubricant on each type of GL. Different GL types obtained using different manufacturing methods (agitated granulation, GL-AG; spray-dried granulation, GL-SD; fluidized bed granulation, GL-FB) were blended with maize starch, low-substituted hydroxypropyl cellulose, and paracetamol in a V-type blender for 10 min. Mg-S was added at varying amounts (0.1, 1.0, and 2.0%) and blending times (5, 10, and 30 min) for the nine types of blended powders for tableting formulation. The powders were tableted, and the tablets were evaluated for weight and drug loading variations, tensile strength, friability, and disintegration time. When tablets with the same blending conditions were compared, the tensile strength and disintegration time were in the order of GL-FB > GL-SD > GL-AG. For each GL, we analyzed the effects of changes in the added amount of Mg-S and blending time using contour plots, evaluated the effects of blending conditions on tablet properties, and determined the target tablet properties. We investigated the optimization of the lubricant blending conditions to obtain suitable tablets.

Evaluation of Sucrose Fatty Acid Esters as Lubricants in Tablet Manufacturing.

Lubricants are essential additives in tablet formulations. Magnesium stearate (Mg-St) is the most commonly used lubricant in tableting. Here, we used sucrose fatty acid ester (SE) as an additive to manufacture tablets by direct compression. We evaluated the effects of hydrophile-lipophile balance (HLB) and the amount of SE on the flowability of a pharmaceutical powder using angle of repose and practical angle of internal friction measurements. In addition, we investigated the effects of SE on tablet properties. When SEs with an HLB ≥3 were added, the angle of repose was approximately the same as that of a pharmaceutical powder containing Mg-St, with no major differences in flowability. However, the practical angle of internal friction became closer to pharmaceutical powder containing Mg-St as HLB decreased. As HLB increased, the practical angle of internal friction approached the value of additive-free pharmaceutical powder. Tablets containing 2.0% Mg-St had a mean hardness of 40 N and disintegrated in approximately 6 min, whereas tablets containing 2.0% SE (low HLB) had a mean hardness of approximately ≥80 N and disintegrated within 3 min. The results indicate that SEs can be used as lubricants in tablet production by direct compression and to reduce problems associated with the use of Mg-St. In particular, we suggest that SEs with low HLB values can be used as excipients to achieve high tablet hardness and short disintegration time.

Setting Ideal Lubricant Mixing Time for Manufacturing Tablets by Evaluating Powder Flowability.

We investigated the effectiveness of using Carr's flowability index (FI) and practical angle of internal friction (Φ) as indexes for setting the target Mg-St mixing time needed for preparing tablets with the target physical properties. We used FI as a measure of flowability under non-loaded conditions, and Φ as a measure of flowability under loaded conditions for pharmaceutical powders undergoing direct compression with varying concentrations of Mg-St and mixing times. We evaluated the relationship between Mg-St mixing conditions and pharmaceutical powder flowability, analyzed the correlation between the physical properties of the tablets (i.e., tablet weight variation, drug content uniformity, hardness, friability, and disintegration time of tablets prepared using the pharmaceutical powder), and studied the effect of Mg-St mixing conditions and pharmaceutical powder flowability on tablet properties. Mg-St mixing time highly correlated with pharmaceutical powder FI (R 2 = 0.883) while Mg-St concentration has low correlation with FI, and FI highly correlated with the physical properties of the tablet (R 2 values: weight variation 0.509, drug content variation 0.314, hardness 0.525, friability 0.477, and disintegration time 0.346). Therefore, using pharmaceutical powder FI as an index could enable prediction of the physical properties of a tablet without the need for tableting, and setting the Mg-St mixing time by using pharmaceutical powder FI could enable preparation of tablets with the target physical properties. Thus, the FI of the intermediate product (i.e., pharmaceutical powder) is an effective index for controlling the physical properties of the finished tablet.