AAPS, San Antonio (Oct. 30)—Aiming to provide a greater understanding of coating processes, speakers at the 20th Annual Meeting of the American Association of Pharmaceutical Scientists presented some of the difficulties, tools, and strategies for obtaining adequately uniform films in pan and fluid-bed coating processes.Uniformity in pan-coating processes
In a presentation titled “Achieving Uniformity Consistency in Pan-Coating Processes,” Stuart C. Porter, PhD, president of Porter Pharmaceutical Technologies (PPT), a consulting services company, provided an overview of the pan coating process and presented modeling techniques and the value they have in understanding uniformity.
Porter introduced the concept of achieving “adequate coating” rather than perfect coating with the key objectives of minimizing tablet-to-tablet variability, minimizing defects such as logo bridging, and maximizing coating functionality.
“Understanding the coating process takes into account process thermodynamics and its impact on coating process efficiency, structure, and functionality; spray dynamics and the uniformity of coating distribution, and tablet movement,” said Porter. In particular, the industry has a “very poor understanding of spraying,” he said. “No two spray guns are exactly alike because of wear and tear of the instrumentation. Also, there are differences in droplet sizes and solids content.”
The consequences of non-uniform coating include visual defects such as variations in appearance as well as variations in functionality such as drug-release performance and stability. For this reason, manufacturers must understand that coating uniformity depends on several factors: the amount of coating picked up while tablets are in the “spray zone,” tablet orientation, and the number of times tablets pass through the spray zone.
Various techniques can be used to improve coating uniformity, and Porter’s presentation focused on two: a statistical design of experiments to assess process impacts on coating uniformity and modeling tools that can improve understanding of the coating process. To demonstrate the utility of a good design of experiments, Porter presented experimental results of the effects of process variables such as pan speed, inlet temperature, and the number of spray guns and on coating uniformity. The study suggested that shallow bed depths, a large number of spray guns, and fully optimized baffle systems produce the best coating. He did caution that results at the lab scale are typically better than at larger scale. “You are likely to achieve the best coating on a small scale, but results may worsen as the process is scaled up. Therefore, process transfer is critical,” he said.
Coating modeling tools
Porter presented applications of modeling tools, including partial least squares modeling used to predict film growth during coating and a discrete-element coating simulation used to analyze how well the coating wraps around a tablet and predict coating uniformity. Digital video analysis (DVA) also was demonstrated to monitor tablet bed dynamics and monitor tablet orientation. “DVA allows us to gain insight into intra-tablet variability of film thickness, or band-to-cap ratio,” said Porter.
The DVA experiments showed, for example, that intra-tablet variation stems from uneven surface-exposure times. DVA can also reveal trends in a tablet’s “orientation index” (OI): Porter observed that OI increased as pan loading increased; OI increased with more mixing elements; OI increased when airflow was reduced; and OI is influenced by pan speed.
Among the conclusions, Porter pointed out that the challenges in achieving adequate coating in coating pans are greater than those in fluid bed processes.Fluid-bed coating
Referring the audience to a Pharmaceutical Technology article published by K. Mehta (Feb. 1988), Grant Heinicke, PhD, Actavis (Iceland, www.actavis.com) first provided an overview of the fluid-bed coating process. “There are generally four types of ‘uniformity’ in manufacturing,” he said: uniformity within the product’s life cycle, uniformity within a batch, uniformity at various dose levels, and uniformity of individual pellets. Heinicke showed results of coating two pellets of different morphologies (one being more nearly spherical) and compared their release-fraction-versus-time profiles and with image analyses. He also demonstrated that increasing computer speeds now make it practical for researchers to use dynamic image analysis methods in the range of 20–50 images per second.