Powder Testing Techniques for Tablet Manufacture

This article considers the different conditions to which the powder is subjected in the tableting process, and discusses which powder properties should be measured to accurately reflect likely powder behavior in the process.
Mar 01, 2012
Volume 2012 Supplement, Issue 2

In tablets, the active pharmaceutical ingredient (API) is often only a tiny proportion of the finished product. The steps that precede the tablet press are designed to incorporate the API within a blend that processes efficiently to produce tablets of the required quality. Excipients include fillers, as well as components that play a more active role in processing, such as glidants to improve powder flow and lubricants that reduce ejection force and prevent adherence to the press.

These raw ingredients may be screened, granulated, dried, milled, classified and blended, often in a number of steps, to produce feed for the tablet press. Batch processing, in which a defined amount of material is processed and then tested to confirm its suitability for the next step, is common.

Each ingredient and unit operation is a potential source of variability arising from any number of factors including:

  • Raw materials
  • Human intervention (especially if the plant is manually controlled)
  • Sampling and analytical test method variability
  • Environmental influences
  • Process equipment capabilities and calibration limits (1).

Materials are tested after each processing step with the aim of quantifying variability, which raises the question of how to characterize "in-process" materials to ensure success. Because the tablet press is at the end of the line, any sources of variability along the way will tend to act cumulatively at the tablet press.

Effective management of variability relies first on being able to detect a problem. This means that a specification used to define acceptability—in a feed or after a processing step— must reliably identify a material that will fail to process as required in a subsequent step or that will go on to produce a substandard product. Such specifications must be based on properties that closely correlate with the aspects of performance that are critical to success. This approach relies on identifying and measuring powder properties that have a defining influence on the efficiency of the operation and the quality of the final product.

Analyzing the tableting process

Powder behavior is influenced by an array of different variables, including primary parameters such as particle size and shape, as well as system factors such as extent of consolidation and aeration. This complexity makes it difficult to predict behavior. To develop a secure basis for process optimization, it is necessary to select powder property characterization techniques that simulate the process environment, because it is difficult to reliably infer performance from test data acquired under conditions that are not representative of those applied during processing.

Manufacturing tablets from a blend tends to be a single integrated process. However, closer analysis reveals four distinct stages, particularly in terms of the conditions applied to the powder. These are:

  • Discharge from the feed hopper
  • Flow into and through the feed frame
  • Die filling
  • Compression, followed by ejection.

Hopper discharge. Tablet manufacture begins with discharge of the blend from the hopper, ideally at a consistent, controlled flow rate. Material flows under gravity, at relatively low flow rates, into the feed frame. In the hopper itself, moderate stress is imposed by the weight of the stored powder. The resulting consolidation may inhibit flow, either because of interactions between the vessel and powder or as the result of powder-powder interactions. Shear strength and wall friction are therefore highly relevant powder properties.

Figure 1: More permeable powders tend to flow consistently from a hopper, while those that are less permeable can give rise to a low rate, ’pulsing’ flow that is detrimental to process efficiency and product quality.
Feed frame flow. The hopper discharge is routed to the feed frame via enclosed pipe work that provides containment. The ease with which the blend flows under gravity is important here, but so too is the permeability of the powder (2). A blend with low permeability that resists the backflow of air necessary for smooth flow will tend to pulse or 'slug' into the feed frame (see Figure 1). This can result in erratic pressure that varies at a relatively high frequency. The tablet press weight control system cannot adequately compensate, which results in variable tablet weight. In contrast, more permeable blends tend to exhibit more consistent flow, ultimately delivering a more uniform density to the feed frame and a more consistent final product.

Die filling. From the feed frame, powder is swept into the dies to ensure a complete fill. Here the blend is moderately to loosely packed, but sheared at relatively high speeds as the paddles of the frame rotate. Agglomeration and attrition are both potential problems, exacerbated by the need to recycle powder around this part of the process. Both can lead to segregation of the blend, giving rise to non-uniformity in the finished tablet. Attrition additionally gives rise to dusting, creating fines that can compromise processing efficiency and the properties of the finished tablet.

In the feed frame, the powder flows under gravity but, depending on the design of the paddles, there may also be a significant element of "forced flow." Angling the sweeping paddles can help to force the powder down into the dies to improve filling efficiency. While optimizing the flow regime in the feed frame improves consistency and the rate of die filling, doing so relies on understanding how the powder flows under different conditions and, in particular, the material's response to forcing conditions.

In addition, the response of the powder to air is critical for consistent die filling. A permeable blend that quickly releases entrained air will settle rapidly and efficiently fill the die. Simultaneously, air can provide lubrication and promote flow in the feed frame. Therefore, a material that releases air too easily may not flow consistently. Understanding exactly how the powder responds to air can be critical in optimizing die filling.

Compression. During the final compression step, the powder plug is subject to high stress. Here, the compressibility of the powder is relevant because it quantifies how the movement of the punches will impact the powder. In addition, adhesivity indicates how likely it is that material will stick to the tablet press tooling.

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