An Automated, Quantitative Method For Stability Evaluations Of Pharmaceutical Emulsions And Solutions
By Justin Hardwick, Research Engineer, Micromeritics
A vital step in determining whether a drug is fit for human use is stability testing, which certifies the drug can maintain its safety and efficacy throughout its proposed shelf life. This includes exposing it to certain storage conditions within its final container. In the current environment of stability testing, the traditional method for determining the presence of foreign particles is simply a visual examination. Yet, in working toward the highest level of safety, quality, and efficacy in drug development, manufacturers must make the move from relying on qualitative, user-dependent results to implementing a fully traceable, analytical, and quantitative method now available in today’s market.
Stability Testing Of Today’s Drugs
There are many types of formulations in everyday life, whether they are lotions, toothpaste, food, or pharmaceutical drugs. Regardless of what the solution is, it is essential that the components in a formulation do not separate. With pharmaceuticals, though, preventing separation of a formulation is critical, as it can result in the components compacting together and not re-dispersing properly even when a vial is shaken. This is applicable to a wide range of pharmaceutical products, such as vaccines, proteins, inhalers, and even gel formulations. The result of a formulation not re-dispersing properly particulates in the drug, which can not only reduce its efficacy but also pose serious risks to the safety of a patient once injected.
To check for the presence of particulates, formulation specialists will conduct stability tests by putting the solution in a vial, mark where it is filled to, and let the vial sit on a shelf (or, for temperature-sensitive drugs, in a temperature controlled room/unit) for a predetermined amount of time to see how long it takes for destabilization to occur. There are three mechanisms of destabilization:
- Sedimentation – when particles sink to the bottom of the vial, making a clarification layer toward the top.
- Creaming – the formation of bubbles that rise to the top of the vial.
- Coalescence/Flocculation – particles that combine and increase over time eventually becoming large enough to sink to the bottom. The reaction can happen alone or it can result in a creaming/sedimentation phenomenon.
The type of destabilization that occurs depends on the solution. Any layers that form during destabilization are marked, and certain factors are analyzed to determine the formulation’s stability. For example, how quickly bubbles take to appear and become bigger. When they do, a drainage layer at the bottom forms. The height of that layer and how much it increases over time should be tracked. Particle size may even be measured to determine emulsion stability. Some formulations can take weeks or even months before destabilization can be seen with the naked eye.
One of the main challenges of stability evaluation is that it is subjective, based on what one person believes they see versus another, which leads to a lack of consistent data. With a better solution, formulation scientists can gain a better understanding of the destabilization factors for their formulation and ultimately create a more stable and reliable product in a shorter amount of time.
An Alternative Solution For Stable Analysis Of Liquid Dispersions
To help identify and solve stability issues in liquid dispersions, Particle Testing Authority (PTA), Micromeritics’ ISO17025 accredited contract testing laboratory, has introduced the TURBISCAN® TOWER. This unit can analyze up to six samples simultaneously for full characterization of the colloidal stability of concentrated dispersions. Operators simply place a 20 milliliter glass tube filled with the solution or emersion in the instrument, where three separate detectors—on the back end, directly across from the laser, and beside the laser—scan the formulation over time using multiple light scattering measurement to detect small changes in movement and, eventually, what type of destabilization occurs. The fully automated TURBISCAN TOWER works for both opaque and transparent solutions as well as diluted samples.
Once the glass tube is placed in the TURBISCAN TOWER, the device’s arm scans up the height of the sample taking a reading every 10 microns, providing a high-resolution representation of the height of the column and any changes in either the transmission signal or backscatter. Each scan can be set to run at specified intervals, and each scan shows the change in the particles within the suspension over time. For example, if the backscatter signal increases toward the bottom of the sample and decreases towards the top of the sample, that means the particles in this solution are settling toward the bottom. The TURBISCAN TOWER’s ability to accurately determine and quantitively measure the stability of formulations provides scientists more insight into not only when destabilization occurs but also what mechanism caused it. Rather than using trial and error to determine a formulation’s stability, the TURBISCAN TOWER provides a unique perspective, allowing them the information necessary to quickly reformulate a solution to achieve the desired shelf life of a product.
Since the release of the TURBISCAN TOWER in 2014, a TURBISCAN Stability Index (TSI) has been adopted by the academic community and documented in various published papers.1 The TSI is a range of numbers used to indicate the stability of a sample in its entirety. The higher the TSI number, the lower the stability. The TURBISCAN TOWER’s ability to efficiently track and measure destabilization using a trusted measurement scale can reduce the time period for testing from months down to days. And as the pharamaceutical landscape continues to grow rapidly, easy-to-use tools and references for stability measurement, such as TURBISCAN TOWER and the TSI, are the types of solutions that will facilitate manufacturing and bring life-saving drugs to patients faster.
- Formulaction. (2012). Applications Overview, Physical Stability of Pharmaceutical Dispersons