Tablet sticking, in which material adheres to the surface of a tablet-punch face, is a perennial problem that causes defects in pharmaceutical tablets, reduces output, and results in press downtime. Tableting experts have developed an understanding of the causes of sticking and have an array of solutions, but finding the best solution can be a time-consuming process. Experts are currently working on further increasing the fundamental understanding of the underlying causes of sticking. This understanding can be used to develop predictive models to more quickly find solutions to specific sticking problems.
Tooling supplier I Holland's Tableting Science Anti-Stick Research (TSAR) program, in collaboration with the University of Nottingham’s School of Pharmacy and experts from the Laboratory of Biophysics and Surface Analysis in the UK, is developing a predictive tool to identify the best punch or die-coating solution to prevent sticking in a given formulation. "Each sticking problem is unique and a specific solution must be found for each formulation," notes Rob Blanchard, research, development, and quality systems manager at I Holland. He explains that, currently, the performance of each coating is field tested against a problematic formulation, and offsite testing is used to identify the best solution. This process, however, is costly and time consuming for the customer. The predictive tool developed through the TSAR project will eliminate these problems by providing quick guidance without time-consuming tests. In the first year of the two-year TSAR program, researchers used analytical techniques (e.g., atomic force microscopy and time-of-flight secondary ion mass spectrometry) to perform adhesion mapping, which chemically analyzes the particles adhering to a punch tip to better understand the interactions that cause sticking. These data are now being used to develop the predictive tool. Researchers also compressed tablets with various formulations using different punch-tip coatings; these experiments will be used to validate the predictive tool at the end of the process in the coming months.
The Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) at Rutgers, the State University of New Jersey, has developed mechano-chemical models and computational methods that predict the evolution of micro-structure and interparticle forces during powder compaction (1). Powders with sticking and picking tendency show adhesion of powder to die walls and tool surfaces. “This can be explained by a competition mechanism between inter-particle bonding and particle-wall adhesion,” says Alberto Cuitino, a C-SOPS researcher and Rutgers professor. He explains that, during ejection of the tablet from the die, the weaker links will naturally break first, resulting in either sticking/picking (if particle-wall adhesion is stronger than inter-particle bonding), internal cracks (if particle-wall adhesion is weaker than most inter-particle bonds), or no defectology (if enough bonding strength was developed during compaction). “These competing effects can be quantified if the network of particle-particle and particle-wall forces are known, which is unfortunately not possible with current experimental techniques,” says Cuitino. The computational models developed at C-SOPS can be used as cost-effective tools to understand and predict the impact of manufacturing process variables on product performance.
Tooling supplier Natoli, a member of the C-SOPS consortium, has already used some of the fundamental information developed at C-SOPS on the role of surface energy in the compaction process and optimal tablet shapes to help solve sticking problems, says Charles Kettler, director at Natoli. Last year, Natoli announced the creation of the Natoli Institute of Industrial Pharmacy Development and Research, in partnership with Long Island University's Arnold and Marie Schwartz College of Pharmacy, to further develop fundamental understanding of tableting problems and formulation studies. Laboratory facilities for the Institute are currently being constructed at the university, and are expected to open late this year with fully qualified equipment. One of the Institute's projects will use a unique screening method developed by Pfizer (2) to screen for the sticking tendency of formulations at or prior to the clinical scale. “This method is a way to test small amounts of API with a given tablet design and tool steel and coating for propensity to sticking for a given API and formulation,” explains Kettler.
1. M. Gonzalez and A. M. Cuitino, J. Mechanics and Physics of Solids 60 (2) 333-350 (2012).
2. M. Mullarney, B. MacDonald, and A. Hutchins, Pharm. Tech. 36 (1) 57-62 (2012).