Effect of additives and operating conditions on tablet weight variation: Analysis based on powder flowability

Abstract

The flowability and compressibility of powders during tableting are crucial for determining the quality of pharmaceutical products. Although silicon compounds are additives that improve compressibility, their type and addition ratio could impair flowability. Therefore, formulation and operating conditions for tablet preparation should be considered. In this study, first, the physical properties of the four types of silicon compounds, that is, particle size distribution, packing fraction, and cohesion, were measured. Next, various powder mixtures were prepared by adding each silicon compound to a diluent at different ratios. Experiments were performed by changing the operating conditions of a rotary tableting machine equipped with a paddle feeder. The tablet weight variation increased with the addition of a highly cohesive silicon compound. However, this variation decreased with an increase in the peripheral velocity of the paddle. A flowability index combining static and dynamic friction properties was proposed to analyze the experimental results, allowing the quantification of the effects of silicon compounds and operating conditions on tablet weight variation.

Introduction

The direct compression method is widely used in tablet manufacturing because of its simplicity and cost-effectiveness. However, the limited process options associated with this manufacturing route render the optimization of the formulation and compounding critical [1]. Diluents have been designed to provide adequate tabletability. Lactose is one of the most widely used diluents due to its easy availability, cost-effectiveness, bland taste, low hygroscopicity, excellent physical and chemical stability, and water solubility [2]. However, when these diluents do not provide the desired effect, additives are used depending on the type and amount of active ingredient. Silicon compounds have been used as additives, and even small amounts (less than a few wt%) can enhance tabletability [3], [4].

Although small-particle silicon compounds are particularly effective, their excessive addition can impair powder flowability [5], [6], [7]. Flowability is influenced by the type of silicon compound and mixing conditions [8]. Low flowability into the die results in insufficient compressibility and tablet weight variation [9]. Factors such as particle size, shape, density, and surface friction considerably affect powder flowability. The mean and distribution of each factor also affect powder flowability [10], [11], [12]. Given the complexity of these factors, predicting flowability by considering individual factors is challenging; therefore, flowability testing is essential.

Conventionally, the angle of repose and Carr compressibility are typically used as indices to evaluate powder flowability [13]. However, with the advancement of tablet design using the direct compression method, the development of a novel method for evaluating flowability is crucial. In addition to measuring the angle of repose and Carr compressibility, many industries that handle powders perform various flowability tests. For example, shear tests are used to evaluate the mechanical properties, such as the yield locus, critical state line, angle of friction, shear cohesion, and flow function, of consolidated powders [14], [15], [16]. Rotating drum tests are used to evaluate the dependence of the rotational speed of the powder bed and the cohesion associated with the powder flow [17]. Powder rheology tests are conducted to measure the torque acting on blades rotating in a powder or fluidized bed [18], [19].

Vibrating tube tests are conducted to evaluate the differences in flowability related to static and dynamic friction. These differences can be distinguished by measuring the critical conditions under which a small amount of powder begins to discharge from a small area because of vibrations and the mass flow rate at discharge [20], [21], [22]. Powders with significantly lower flowability, such as nanoparticles and fibrous particles, require larger external forces that combine vibration and shear fields [11], [23], [24]. Furthermore, numerous other flowability tests have been proposed [25]. However, because each test has a specific range of applications [26], the test method should be selected according to the processing conditions to which the powder is subjected. Because tableting involves filling the die with a small amount of powder, the vibrating tube or vibrating shear tube method is appropriate for evaluating flowability under such conditions [5], [8], [11], [12], [22], [24].

Rotary tableting machines are used in pharmaceutical industries to emphasize production efficiency. Die filling occurs when the powder mixture passes over the die. Experimental devices that reproduce a series of movements of rotary tableting machines have been used to study the behavior of powders [27], [28], [29]. Studies have investigated the effects of the particle diameter and density on die-filling performance [30], [31]. Paddle feeders have been used to increase die-filling performance, and their operating conditions and equipment geometries have been studied comprehensively [32], [33], [34], [35], [36], [37], [38]. In addition, discrete element method simulations have been used to analyze the powder flow [39], [40], [41], [42]. After improving the production efficiency, the issue is to ensure the quality stability of tablet weight.

Tablet weight variation has been analyzed for mini-tablet production [43], [44] and continuous manufacturing [45], [46]. Sparse modeling has also been proposed to select the flow properties necessary for predicting the tablet weight variation [47]. However, detailed studies analyzing the tablet weight variation for powder mixtures containing silicon compounds based on the results of rigorous flowability tests are yet to be reported.

In this study, various powder mixtures were prepared by adding silicon compounds with different cohesion properties to the diluents. The operating conditions of a rotary tableting machine equipped with a paddle feeder were varied, and the tablet weight variation was analyzed based on flowability. The vibrating tube method, which distinguishes between static and dynamic friction properties, was used to investigate flowability.

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Raw materials

Milled lactose powder (Lac: Pharmatose®150 M, DFE Pharma, DEU) was used as the diluent. Aluminum silicate (AS: synthetic aluminum silicate (extra light), Kyowa Chemical Industry Co., Ltd., JP), magnesium aluminometasilicate (MA: Neusilin®UFL2, Fuji Chemical Industries Co., Ltd., JP), magnesium silicate (MS: magnesium silicate (light), Kyowa Chemical Industry Co., Ltd., JP), and silicon dioxide (SD: Adsolider®101, Freund Corp., JP), were used as additives to increase tablet hardness. Magnesium stearate.

Yozo Kudo, Tsukasa Nakanishi, Akira Uno, Shuji Matsusaka, Effect of additives and operating conditions on tablet weight variation: Analysis based on powder flowability, Advanced Powder Technology, Volume 36, Issue 6, 2025, 104860, ISSN 0921-8831, https://doi.org/10.1016/j.apt.2025.104860.

Read also our introduction article on Magnesium Stearate here: