Evaluation of Automation to Increase Efficiency in the Dissolution Lab

Abstract

This paper presents a comprehensive evaluation process and implementation case study results for the migration of a pharmaceutical development dissolution testing laboratory to fully automated systems to improve efficiency. Three classes of dissolution systems were evaluated: manual dissolution baths, ultraviolet (UV) online systems, and fully automated systems. The comprehensive analysis clearly shows that the fully automated system requires the lowest total analyst time to perform the dissolution experiments. Also presented are several additional factors to consider when evaluating the right type of dissolution system for a particular lab. The results of this case study show the benefit of using a fully automated dissolution system for a design of experiment (DOE) study. INTRODUCTION The pharmaceutical industry is in the midst of one of the greatest periods of change in its history. With health insurance reform reducing the pricing of drugs for pharmaceutical companies and the increased demands of clinical trials, the return on investment for research and development is steadily decreasing. As a whole, the industry has been driven to find new ways to reduce cost and rethink its strategy. Every department from the top down has been tasked with finding ways of being more efficient in this new era. Automation in the pharmaceutical development laboratory offers great potential for increased efficiency and reduced laboratory errors, and has been a topic of recent interest. In this paper, the writers discuss the evaluation process and preliminary implementation results for a pharmaceutical development laboratory to migrate dissolution testing toward fully automated systems to improve efficiency. EXPERIMENTAL First, we must define the pharmaceutical development laboratory for the purpose of this discussion. The typical pharmaceutical development laboratory contains a wide variety of instruments spanning multiple functions and platforms. The scientists in these labs perform a variety of roles rather than specializing in a single discipline, such as dissolution testing or assay testing. This is important to consider since a scientist in the laboratory may only perform dissolution testing once every month or longer and would not be expected to be as efficient as a scientist dedicated to dissolution testing. It is also important to note that the dissolution footprint is not as large as in a dedicated high-throughput dissolution laboratory. The number of dissolution baths are limited and divided between GMP and non-GMP usage. Second, we must define the dissolution systems that we evaluated to find the best fit for our lab. The first system was the manual dissolution bath (e.g., Distek Evolution 6300 with a syringe autosampler or Agilent VK7025 with a peristaltic autosampler). The second system can perform UV online testing (Distek 6300 with Agilent UV 8453 or Agilent VK7025 with Cary 50 UV). The third system was a fully automated Sotax AT-70 system. The writers will discuss their views on the pros and cons of each of the three systems in the evaluation. Note that numerous other instruments that behave similarly to each of these instruments, as well as other systems (such as fiber-optic), are not discussed due to time and length restrictions. This evaluation is for our particular type of pharmaceutical development laboratory. It is very possible that a different type of lab (e.g., high-throughput) will have different objectives and considerations. So when reading this paper, please consider our recommendations in their context and evaluate whether they could be applicable to your specific laboratory environment. Lastly, we must define the dissolution test scenario that was applied to each of the systems for a fair comparison. The test was conducted using USP Apparatus 2 (paddles) at 75 rpm. The medium was 0.05 N HCl. Four samples were tested at n = 6. The time points were 5, 15, 30, 45, and 60 min. The filter was a 10-μm, full-flow filter. The sample volume was one milliliter. The samples were analyzed using either high performance liquid chromatography (HPLC)– UV or UV online. Manual Dissolution Bath Setup When setting up the manual baths, there are a number of factors to consider when determining how many baths to run. Generally, the number of baths and the number of HPLC instruments available are the biggest limiting factors. Another factor is whether the time points are too close together to manually sample. The use of autosamplers makes this limitation void for most tests since they are usually set up one per bath or one per two baths. Using the rule of thumb of two baths per HPLC, our test *Corresponding author. e-mail: jkretz@amgen.com dx.doi.org/10.14227/DT200213P33