Developing a formulation for solid oral dosage that can be compressed in a modern tablet press, and at high speed can cause a number of technical challenges, and many of these are down to the physical content of the formulation being used from moisture content to abrasiveness. The tooling used needs to reflect the formulations being compressed to ensure a quality fault-free end product.
Tooling and its related equipment must be chosen according to the formula being used and proper tooling maintenance and standard operating procedures should be adhered to reduce the many variables affecting tablet manufacture. Here we take a look at the most common problems with formulation composition and how they affect production.
Fines
One of the first considerations is if the formulation being used contains very small particles. If it does then the clearance between the tip of the punch and the bore of the die is critical. If the clearance is too large, then the smallest fines of the formulation can pass between the punch and die. This can cause several problems including binding and tightness of the punch tip in the die bore. This, in turn, generates friction and heat which can cause abrasion of both the die bore and the punch tip resulting in die bore ringing and tip abrasion resulting in flashing around the circumference of the tablet.
Fine particles can also pass through to the lower punch guide seals. If these are not sufficiently fitted or worn, further tightness and wear can be generated between the punch barrel and lower guides. Fines can also cause a general contamination issue as they are more easily airborne and can penetrate upper guides with similar results
if seals and bellows are not used and maintained correctly. Excessive fines will result in poor tablet quality, as well as tool binding and tablet press overheating, which increases sticking and picking issues.
Moisture
Moisture within a tablet is often needed to help the binding effect but this can also be a root cause of sticking. When the adhesive forces of the formulation to the punch tips overcome the cohesive forces within the tablet, then sticking can occur.
Water within the tablet can be one of the causes of a rise in adhesive forces. This happens by the increase in capillary action between the tooling surface and the granule. Capillary bridges form causing high adhesion areas, thus creating sticking. Moisture can enter into the process either in wet granulation or due to excess humidity in the compression chamber in a non-environmentally controlled area; the latter can even affect direct compression formulations.
One solution would be the use of anti-stick coatings applied to the tooling which repel rather than attract moisture but the selection of the right coating for the job is a specialist one which not all tooling manufacturers are equipped to undertake.
When coatings are developed correctly, and their beneficial characteristics are matched to those of the formulation, they can help to increase corrosion resistance, wear resistance and prevent sticky formulations adhering to the punch tip faces. Traditionally, the most popular coating used within the global tablet tooling industry is hard chromium, due to its low cost and general purpose characteristics in terms of average anti-stick, anti-corrosion and anti-wear properties. There are, however, many options out there, one of the most recent additions to the I Holland portfolio is PharmaCote® CT (Textured Chromium Nitrate). This exclusive surface treatment, combined with its proven PharmaCote® CN anti-stick coating, generates an anti-stick tip face for tablet production and also shows good corrosion resistance in intensive salt spray tests, as well as good wear resistance.
Abrasive
Some formulations contain ingredients which are particularly hard and sharp. Typically (but not exclusively) these are found in nutraceutical products which contain many minerals and hard organics. Through repeated cyclic compression, these abrasive ingredients can wear away both the surface of the punch tip and the bore of the die, resulting in low quality tablets. Hard granules can even impregnate the surface of the punch tip under high compression forces. These actions can then lead to other tabletting problems such as capping or de-lamination and sticking. This abrasive action can be countered by the use of advanced tooling materials and coatings selected for their wear resistant properties. Materials such as I Holland’s specialist steels used in conjunction with resilient coatings like I Holland’s PharmaCote RS or tungsten carbide dies have high hardness values and specific structures which abrade at a much lower rate. In some cases, tool life has been increased by 700% over a standard steel tool.
Corrosive
Certain constituents of the formulation can contain corrosive elements such as chlorine, salts and acids which will react with the tooling surfaces and result in oxidation. In addition, wash in place systems fitted to some modern tablet presses expose tooling to water and cleaning solutions, therefore, they require tooling to have good corrosion resistant properties.
Indeed post compression cleaning procedures can also cause corrosion, if not controlled sufficiently. Corrosion can appear as discolouration, etching or common red rust. To combat this issue, a corrosion resistant material can be selected; however, standard stainless steel types are not suitable due to lack of hardness and wear resistance. Therefore, specialised Martensitic stainless steels with high chromium content should be used. It is also possible to apply hard coatings with corrosion resistant properties such as hard chromium or chromium nitride.
Deformation Characteristics
The characteristic of certain ingredients in a formulation can have plastic or elastic properties leading to tabletting issue such as sticking and capping. Where the behaviour of a particle under compression can either stay deformed or ‘spring back’ to its original shape, the dwell time of the machine can be critical. In cases of formulations with more time dependant consolidation behaviour, a long dwell time is important to create strong bonds between the particles. In a situation whereby a greater dwell period may be required, there are tools on the market to help including I Holland’s new innovative extended dwell flat tooling (XDF) which will enable a suitable compression dwell time for a formulation without the disadvantage of slowing the press.
Friability
Friability, or the tendency to crack, chip or break during compression is in part due to the formulation. If the formulation is not cohesive and does not bind together sufficiently, then friability will occur. There are several ways to compensate for friability including looking at dwell time, weight control, expansion and of course tooling condition. All of these should be examined to produce a quality tablet.
How to produce a fault free tablet?
The development of formulations for solid-dose products can be a complex and problematic procedure; however, with certain considerations and measures in place, it can be achieved successfully.
Pharmaceutical formulations normally contain one to four actives and five to six excipients. This can bring challenges related to particle size, flow, compressibility, interaction, content and uniformity. For example, some active ingredients may be available in granular form, while others may be available only in fine powder form; some may be hydrophilic and others hydrophobic. Because of this, the ingredient blend may have many different particle sizes and ingredients with a variety of characteristics.
Some formulations can cause adverse effects on the punch tips when under compression, such as abrasion, pitting or corrosion. Although tools are manufactured from hardened and tempered tool steel, the demanding processes involved can lead to deterioration if the tool material is not optimised to suit the formulation being compressed. Some granules are extremely hard and abrasive and can scratch, wear and impregnate the steel surface. Other granules can contain corrosive elements which react with the steel.
These effects can be reduced by understanding the nature of the formulation to be compressed and carefully selecting a material or tool coating to resist this.
The important message here is that it is important to talk with an experienced tooling equipment supplier if you have manufacturing problems as they can pin-point exactly what the problems are and offer a resolution. This in turn reduces costs through production downtime. Today, in order to produce mass robust tablets with tailor-made properties, every process must be considered, and that includes the formulation being used.
