Thursday, April 15, 2021

Cracking in Tablet Manufacturing: Causes and Remedies

by | February 28, 2021 0

A major problem that can occur during or after tablet manufacture is cracking. This can manifest itself in a number of ways, depending upon the material properties of the formulation. It can range from surface cracking through to capping and lamination. Capping is when the upper or lower cap of the tablet separates horizontally, either partially or completely, from the body of the tablet. This can occur during ejection from the tablet die or during subsequent operations, such as coating, packing or shipment. Lamination is when cracks form within the body of the compact, resulting in the tablet splitting apart into layers.

Cracking can be caused by a number of factors that may contribute to these problems. One potential cause is the inadequate removal of air from the granules in the die-cavity before and during compression. The initial volume of granules may be several times that of the compact into which they are compressed, particularly for high-porosity granules. During compression both particles and air will be compressed. The reduction in volume is due  to removal of air. This air will need to escape from the compact otherwise there is the potential for this entrapped air pressure to blow apart the compact on ejection. The entrapped air interferes with granule bonding while its subsequent expansion at the ejection stage detaches the cap or laminates the tablet. Air removal can be facilitated by using dies which are tapered outwards toward the top of the die to allow the air to escape. Large numbers of fine particles or too small a top punch/die-bore clearance all hinder escape of air from the die cavity and may be another cause. Fine material can seep downwards through the clearance and compact to form a tough film which hinders free movement of the punch.

Read Also: Common Tablet Defects: Causes and Remedies

For example, if on the punch and die drawings the tooling clearance is shown to be 25 microns and the compression mixture has a large 25 micron component there is the potential for powder to get lodged between the punch and die clearance. Decreasing the tabletting speed will also increase the time available for the air trapped between the granules to escape, thereby leading to the potential for decreased air pressure in the die, particularly for high-porosity beds. high-speed compaction using tooling with deep curvatures, such as are used for coated tablets, contributes to air entrapment at the top punch. hence, using shallower tooling can alleviate this cause of cracking.

A second cause of cracking is associated with undue elastic compression of the tablet due to the use of too high a pressure at the compaction stage. During ejection, elastic recovery of that part of the tablet protruding from the die gives rise to lateral forces, which rupture the intergranule bonds and the tablet then caps or laminates. One source of over compression will occur when the porosity of the formulation drops below 10%. The maximum tensile strength of a formulation is at 15% porosity (which is equivalent to a solid fraction of 0.85). hence, if the desired tensile strength is not being achieved than the main formulation approach would be to increase the binder or compression aid level. In addition, if porosity drops below 15% then water penetration normally becomes harder and so disintegration times become prolonged.

The viscoplastic–elastic behavior of the formulation components may also be a contributor to cracking due to the elastic nature of some of the materials causing the tablet to spring apart. The response is often time dependent. As speed is increased, the relative elastic component of a given material also increases, giving rise to a higher incidence of cracking. Hence as compression speeds are increased, the occurrence of cracking and lamination of compacts tend to become more prevalent. hence reducing compaction speed may help. An alternative processing method of overcoming this and effectively increasing the relaxation time is to use pre-compression prior to the main compression. Most rotary presses have two rollers in series after the die filling step, which apply the pressure to the tablet prior to compressing it. The first roller is a pre-compression roller and the second is the main compression roller. Typically the pre-compression is at 10% of the main compression pressure. However, this is very much formulation dependent. The optimal tensile strength of some formulation being produced from having a pre-compression larger than the main one.

Read Also: 25 Common Practical Questions and Suggested Answer for Tablet Coating

Elastic recovery itself will not necessarily result in lamination. Lamination will only occur if the inter-particle bonding cannot accommodate this elastic recovery. Hence, the formulation options are to either increase the binder level, or change the type of binder in the granule. An alternative approach is to incorporate polymeric materials as compression aids, such as celluloses, which undergo less elastic recovery or which can absorb the stresses. For organic material the moisture content can also be important as the level of residual moisture in a polymer can affect its deformation properties. Typically the drier the material the more brittle it becomes as water tends to have a plasticizing effect.

Unwanted viscoelastic behavior can sometimes be shown by high residual die wall stress. Die wall stress is the force remaining in the tablet in the die after compression and prior to ejection. It is measured using an instrumented die which records the stress exerted by the area of tablet in contact with the die wall (the “belly band”). Residual dies stress values below 20 MPa should be targeted. If high values are obtained then they can be reduced by including auxetic materials, such as low-substituted hydroxypropyl celluloses or modified starches.25 Tapered dies can also be used as they have the advantage of increasing the volume available for the tablet to expand into radially, hence reducing residual die wall pressure.

Sticking of the compact to the die wall or punch components can also induce stresses resulting in cracking and can be controlled by adjusting the lubricant levels. Lubricants will minimize die wall friction and prevent the  adhesion of the granules to the punch faces and, hence, can be manipulated to overcome cracking and lamination. Varying the level of lubricant or the ratio of external to internal lubricant can both help. An alternative approach is to spray the lubricant into the punch and die cavity immediately before die filling and hence directly coat the surfaces of the tooling. This latter approach requires modification of the tablet press. One approach is to spray the lubricant dry into the punch and die cavity. The other approach is to disperse the lubricant into a volatile solvent and to spray the tooling surfaces via a liquid nozzle. Magnesium stearate, as well as other lubricants, has been applied by both methods.

Wearing of the dies bores, particularly by hard inorganic fillers, can also lead to tablet damage. Wear in the dies takes place usually about the point of compression and results in a circular depression within the die. A compact compressed in this cavity has therefore to be forced out through the smaller aperture in the top of the die resulting in shear and lamination. This can be resolved by using wear-resistant steel for the dies or specially hardened die inserts.

Source

  • Tovey, G. (2018). Pharmaceutical Formulation: The Science and Technology of Dosage Forms. Royal Society of Chemistry.



Leave a comment

Your email address will not be published. Required fields are marked *

x