Related reading: Powder Flow: Powder testing techniques for tablet manufacture (2)
Medications in solid dosage form continue to be universally popular, with the majority of pharmaceutical actives still delivered as tablets. Across the globe, tablet manufacturers employ a diverse range of machinery based on designs whose roots can be traced to equipment developed over a century ago. Today’s state-of-the-art tablet presses produce up to a million tablets per hour, but whatever the scale of operation or the machinery used, the fundamental challenges remain the same. Successful tablet manufacture relies on filling a die with a uniform, loosely packed blend and then compressing that powder to form a consistent stable product.
Apart perhaps from a final coating step followed by packaging, tablets are usually the end product of the manufacturing process. This is an important point when considering process optimization as many of the steps in the process are carried out with the aim of delivering a suitable feed blend to the tablet press. These steps may include feeding, screening, mixing, granulation, drying, milling, classification and lubrication.
Variations in any of these unit operations, or indeed variation in the raw materials, can have a contributory effect on the properties of the feed to the tablet press and consequently, may impact on the efficiency of the process. A greater understanding as to which powder properties relate to performance in the press, and indeed which upstream processes are most influential, enables improvements to be made at the appropriate processing stage(s). This leads to improved throughput and enhances the quality of the finished product.
In this article we examine the tableting process, from blend discharge from the feed hopper to ejection of the tablet, and consider the different conditions to which the powder is subjected. Building on this analysis we discuss which powder properties are important in defining performance at each point, highlighting the need to measure variables that accurately reflect likely powder behavior in the process. Included in the article are data that show how different techniques such as tapped density and shear testing, while valuable for specific applications, are less relevant to certain aspects of process behavior.
Preparing a tableting blend
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. Ingredients normally include excipients and fillers as well as components that play a more active role in product performance, such as glidants to improve powder flow and lubricants that prevent adherence to the press.
These raw ingredients may be screened, granulated, dried, milled, classified and blended, in isolation or in combination, to produce feed for the tablet press. Usually this involves a number of steps and batch processing is common, where a defined amount of material is processed then tested to confirm its suitability for the next step.
Each ingredient and unit operation is a potential source of variability arising from any number of factors including1:
- Raw material supply
- Human intervention (especially where the plant is manually controlled)
- Sampling and analytical test method variability
- Environmental influences
- Process equipment capabilities and calibration limits
Within the pharmaceutical industry, materials are tested after each processing step with the aim of quantifying variability, but this raises the question of how to characterize ‘in-process’ materials to ensure success. The tablet press is at the end of the line so any sources of variability along the way will tend to ac...
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