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Different Solutions For Tablet Sticking

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7 September 2016 No comments

One of the major problems that the tablet manufacturing companies faces is tablet sticking. This problem occurs when the granulation sticks to the punch surface causing deformed tablets, which is very costly not only for the manufacturers but also for the formulators. One way to alleviate this problem is using analytical method as well as create screening processes. Authorities or field experts are also looking for ways to create analytical models to identify the solutions quickly for specific problems.

As there are different variables that result to sticking, there are varieties of ways or solutions that one can use to solve the problem. Some variables include the following:

  • Formulation – excipients, APIs
  • Granulation properties – particle size distribution
  • Tablet design – shapes and sizes
  • Tablet press conditions
  • Tablet tool properties
  • Maintenance of tools

Solution to Tooling Problem

Tooling suppliers realize the importance of proper tooling and tooling maintenance in preventing the sticking problem. I Holland in fact recommends the 7-steps in maintaining the tooling quality.

7 Steps to Proper Maintenance

  • Cleaning
  • Wear and tear assessment
  • Repair
  • Measuring to ensure accuracy of the equipment
  • Polishing
  • Lubrication
  • Storage

In order to ensure the quality of the punch, one can use microscopy to check the punch surface. With the use of the tool, one would be able to check for miniscule defects that are otherwise invisible to the naked eye. These miniscule defects can cause hug problems and delay delivery of products. The use of microscopy would allow one to check if the tool has any basic problems. The analysis would help one to know the problem and solution to handle the problem. Microscopy is used to check the punch’s surface. One cannot assess the scratches with one’s naked eyes but the miniscule particles will stick to the surface. These cause film spots to appear and as more powder is added, it would cause defects to the product. The microscopy would enable one to check whether the tool has a problem. The analysis would aid one to identify the cause of the problem.

Tooling vendors have also created a distinctive, special type of steel and coating that prevent the sticking. That said, looking for the right material could be a time-consuming process, which would involve field-testing in the client’s location as well as testing to be conducted in laboratories in order to find a solution to address the problem. I Holland’s TSAR program with collaboration with the University of Nottingham’s School of Pharmacy as well as the experts in the Laboratory of Biophysics and Surface Analysis have been developing a ‘predictive tool’ in order to recognize the ideal punch or die coating solution that would result to the prevention of the sticking of the granulation to the surface. This device would provide the proper tool without time-consuming test.

The TSAR program researchers made use of the Atomic Force Microscopy (AFM) to note the adhesive forces on the tablet punch face. The AFM can expose the chemical and mechanical properties such as elasticity, molecular bond rupture as well as adhesion. The map would show the differences in the adhesion properties, which are caused by the surface topography affected by different coatings, applied at various humidity level.

The TSAR researchers would also use different x-ray equipment such as a.) Time-of-flight secondary ion mass spectrometry, b.) Photoelectron spectroscopy and c.) Raman spectroscopy in order to envision the different chemical patterns of various ions on the surface area and to comprehend the interactions that happened during the sticking.

The Principle component analysis or PCA is a statistical technique, which is being used to analyze and generate data that would explain how adhesion happens when chemicals are exposed to different surfaces. The predictive tool is then validated by the results obtained from compression experiments from various punch tip coatings and formulations.

Even if companies perform regular maintenance, in most cases, the root cause of the problem is the formulation or particle size. If the properties were set, companies would then have no choice but to find the solution in the tooling or press. In certain instances, one would be able to reformulate the formulation in order to achieve a lower probability of the sticking to occur.

Tools for Screening

There are different ways for one to assess the sticking problem and screen the sticking propensity but one is hindered by its complexities. As such, many would rely on visual inspection, which is often subjective, and limits one’s ability to consistently screen. In order to address this problem, Pfizer researchers have developed a simple tool to measure the tablet sticking propensity, which can be used to check the sticking level for different formulations and ingredients. The custom tableting tool has a removable tip, which one can use to measure the amount of adhered powder. The gravimetric method is very successful when it comes to identifying the sticking level during the design stage and has greatly reduced the risk during the scale up. The company can actually customize the API and drug product formulation to make sure that it will not go above the threshold level before volume tablets are manufactured. The screening is also useful for different campaigns such as inspection frequency of tablets as well as in analyzing the main problem of sticking for large-scale companies.

As simpler and less complex tools are now being developed to make screening easier, pharmaceutical companies as well as research groups are now able to focus more on other matters such as the molecular structure and other properties and building prototypes, which can explain the sticking pattern. Later on, one would find out that sticking is composed of several mechanisms and molecular chemistry and bulk characterization tools may be used to identify the different sticking patterns for different powder components. Once addressed and identified, drug formulation may be adjusted to lower the sticking problem. Current research conducted by Pfizer is focused on why some APIs stick more than others; the company is also investigating the effects of solid APIs attributes in relation to sticking. Both the computational and experimental approach is crucial, as it will help the researchers to determine the root cause of the problem. Tooling designs and surface area treatments may also be included in the research.

Tablet Micro Structuring

Building models, which can identify sticking, has now being progressing. Researchers such as Gonzalez, Cuitino of Rutgers and the State University of New Jersey has developed a “mechano chemical model” and a computational model which can calculate the microstructure evolution as well as the inter-particle force that happens during powder compaction. Due to the varying properties of the compacted tablet that can be accredited to the microstructure, these models can then be used as a vehicle to help one to understand and analyze how the process can affect the performance of the product.

As powders have the tendency to stick and ick (which is due to the adhesion of the powder to the die walls and tool surfaces) this can be explained by the mechanism of the inter-particle bonding and particle wall adhesion. If the particle wall adhesion is more resilient than the inter- particle bonding, the fragile inter-particle bonding, will then break when the tablet is ejected which can cause sticking or picking. If the particle wall adhesion is more delicate than the inter- particle bonds, the possibility of internal cracks might occur. If there is enough bond strength during compaction, no defects will occur. That said the network of the particles-particles and particle-wall forces are already known, the competing effects can then be computed. As the measurement is not possible with the experimental procedures used today, the researchers have developed a nonlocal formulation, which can precisely describe the system.

The model is based on the particle mechanics, which defines each particle in the powder as an individual object. The discrete model resolves the rearrangement and the deformation of the powder bed and the microstructure of the compacted specimen is predicted.

External Lubrication

Many tooling vendors have seen an interest in the use of external lubrication in order to eradicate sticking, addressing additional ejection forces or to provide a different way of using the lubricant in the formulation should the lubricant cause problems such as hardness or dissolution. With this method, the lubricant is suspended in the air and sprayed using a nozzle, which is then mounted near the tablet takeoff. A fine layer of the suspension is then sprayed on the exposed upper and lower punch and die wall.

For complex products, the method can lower the possibility of tablet sticking or ejection forces. An example would be tablet geometries that have a vast sidewall surface area, which has high degree of friction amongst the die wall and tablet. The external lubricant is then sprayed on the

die wall in order to decrease friction and eradicate the need for excess ejection forces that can cause damage to the equipment.

To help lengthen the life of the punch head, faces, scrape off bars of tablet presses as well as the ejection cams, one needs to use external lubrication to lower the ejection force as well as the scrape-off force. Aside from this, it can also lower the percentage of broken tablets, which can affect the whole production, and cause downtime and increase production volume.

In certain instances, the external lubrication can decrease ejection force of up to 50%, it also help improve the integrity of the tablet’s outer edge.

That said, the external lubrication may or may not affect other tablets. The lubricating system is also expensive and can be quite complex, aside from additional cleaning requirements. Tablet manufacturers have the option to choose a substitute or alternative solution. Aside from external lubrication, one may also coat the tooling equipment. The lubricating system is not used for all formulation types and has in fact being used for complex tablet manufacturing.

The system can be used if the drug formulation causes problems, an example of which is magnesium stearate, which is not water-soluble and with concentration level of 0.5 -2% can cause hydrophobic bridges, which can delay tablet dissolution. The delay can cause problems with the release of the APIs in the tablet. With the use of the external lubricant, it helped poor soluble APIs. Aside from non-soluble, the system can also be effective for effervescent tablets. The system helps reduce the amount of water-soluble magnesium stearate, which prevents the white film effect.

Other benefits of external lubrication is that it can be used to improve the disintegration or dissolution of oral tablets as in certain cases, internal lubrication can affect the hardness of the tablet. A research done by Pfizer shows that external lubrication can improve tablet’s hardness when compared with internal lubrication when tested using various compression force. The research shows a consistent level of magnesium stearate across the surface of the tablet as well as all over the tablet run.

A simple model was developed by Rutger’s Engineering Research Center for structured Organic Particulate Systems (C-SOPS) where it predicts a compaction curve that shows the pressure that was applied by the upper and lower punches. It also shows the pressure level that the die wall receives as the result of the compression of the powder. The (insert) shows the tablet microstructural details, inter-particles and particle-wall forces.

The computational models can resolve as well as track micro-structural changes that happen to the powder bed that is compacted to relative densities from 1 to 0. Figure 2 shows a compaction curve that is anticipated by the model. The black line correlates to the pressure that is applied by the upper and lower punches in order to achieve a determined relative density. The blue line

on the other hand is the pressure that is being experienced by the die wall as the result of the powder compression.

To measure the material properties used by the model, a tablet press stimulator and hardness test is used. One can use the model to anticipate powder behavior as well as other properties for a given tablet press condition. It also can predict powder formulation, mass and particle-size distribution for each formulation component.

In its early stages, C-SOPS also uses tomography, which measures the density gradient of tablets at different compressions. The measurement can identify near surface defects or internal defects that are otherwise invisible to the naked eyes. The defects can be due to the tooling shape, which after the information is acquired will be used to optimize the punch shape to prevent any defects to areas that are prone to the problem.

Summary

Latest research includes information about adhesive forces and the interaction of particles that would result to sticking. Researchers are still looking for ways to expound on different sticking tools where the results can help the industry find the solution needed to prevent sticking as well as improve APIs formulation.