Pharmaceutical Tablet Manufacturing

Powder compression, the primary technique for tablets manufacturing, involves applying pressure to force particles together in a confined space, creating a porous, solid specimen with defined geometry. This process occurs within a die using upper and lower punches to apply compressive force, resulting in a reduction in volume and the formation of bonds between particles. As a result, a compact, coherent tablet is produced.

Tableting can be segmented into three stages:

Die filling

The process is usually carried out by allowing the powder to flow from a hopper, through the die table, into the die via gravity (Fig. 1.), although some presses utilize centrifugal die filling. The lower end of the die is then sealed by the lower punch.

Pharmaceutical tablets manufacturing
Fig. 1.: Illustrate the die filling process.
Tablet formation

The upper punch descends into the die, compacting the powder until it forms a tablet (Fig. 2.). Throughout this compression phase, the lower punch may remain stationary or move upwards within the die. Once the maximum force is applied, the upper punch retracts, initiating the decompression phase.

Tablet compression in tablet formation. Pharmaceutical tablets manufacturing
Fig. 2.: Illustrate the process of tablet compression.
Tablet ejection

In this phase, the lower punch ascends until its tip aligns with the top of the die. Following this, a pushing device removes the tablet from the die table.

Pharmaceutical tablets manufacturing.Illustrate the process of tablet ejection during tablet formation.
Fig. 3.: Illustrate the process of tablet ejection during tablet formation.

Tablet Compression Machines

Tablet presses are categorized as either single-punch or multistation rotary presses.

Single-punch press

In a single-punch tablet press, one die and one pair of punches facilitate the tablet production process. The powder is contained within a hopper, which is linked to a hopper shoe situated at the die table. This hopper shoe moves back and forth over the die, employing either rotational or translational motion. When the hopper shoe aligns with the die, gravitational forces enable the powder to flow into the die, regulated by the position of the lower punch. Concurrently, as the hopper shoe shifts away from the die, the upper punch descends, initiating the compression of the powder within the die. Throughout this procedure, the lower punch remains stationary, and pressure is exerted solely by the descending upper punch, its displacement precisely managed.

Following compression, the formed tablet is ejected from the die, propelled away by the returning hopper shoe, which then positions itself over the die in readiness for the subsequent tablet formation. This cyclic process ensures the continuous and efficient production of tablets using the single-punch press, streamlining the manufacturing workflow and enhancing productivity. The single-punch press achieves an output of approximately 200 tablets per minute, making it ideal for manufacturing small batches of tablets.

Multistation presses

The multistation press, also known as a rotary press, is a machine designed to increase tablet production. It operates by rotating a head containing upper and lower punches, as well as a die table. Powder is fed into the dies through a hopper and feed frame, with the compression process controlled by cams and rollers.

During operation, the head rotates, guiding punches up and down through fixed cam tracks, controlling filling, compression, and ejection. The upper and lower turrets hold punches, while the die table houses the dies. Granulation from a hopper fills the feed-frame, overspills into the dies, and is then compressed by the punches.

Excess granulation is removed by a wipe-off blade, and compression occurs as upper and lower punches interact with compression rolls. After compression, tablets are ejected, guided by cams and an ejector knob, and collected in a receptacle. The process repeats, ensuring efficient and high-volume tablet production.

Tablet Production and Manufacturing

It can be achieved through two primary methods: granulation and direct compaction.

Tablet production via granulation

Production via granulation involves several steps starting with formulation development, where active ingredients and excipients are blended to create a granulation blend. This blend undergoes either wet or dry granulation techniques to form granules, which are then dried if wet granulation is employed. After drying, the granules are sized and milled for uniform particle distribution. Additional blending may occur if necessary to ensure uniformity. Subsequently, the granules are compressed using a tablet press to form tablets of the desired shape and size. Optionally, tablets may undergo a coating process for appearance, taste enhancement, or modified release characteristics.

Tablet production via direct compaction

Direct compaction in tablet production streamlines the process to just two steps: powder mixing and tableting, significantly cutting production time and costs. However, it necessitates specialized fillers and dry binders, potentially increasing expenses and quality testing requirements. Nonetheless, it enhances product stability by avoiding heat and water, while also potentially improving drug dissolution rates due to faster tablet disintegration into primary drug particles.

The drawbacks of direct compaction primarily stem from technological challenges. Utilizing large particles to maintain acceptable flowability and bulk density can lead to difficulties in achieving high homogeneity and may result in segregation issues. Additionally, tablets composed mostly of a drug with poor compactability pose challenges in tablet formation. Lastly, achieving uniform tablet coloring with dry particulate colorants can be problematic.

Direct compaction offers a practical approach to tablet formulation in two common scenarios. Firstly, for drugs with good solubility, coarse particles can be employed to maintain favorable flowability during processing. Secondly, for potent drugs requiring only a few milligrams per tablet, they can be combined with coarse excipient particles. In this latter case, the flow and compaction characteristics of the formulation are predominantly influenced by the properties of the excipients. This strategy allows for efficient tablet production while ensuring optimal drug distribution and dosage consistency.

Reference:

  • Aulton, M. (2018). Aulton’s pharmaceutics, the design and manufacture of medicines. Edinburgh. : Elsevier