Tank mix compatibility testing is important for determining and predicting issues that could occur with a formulation when used or prepared for use in the real world. Tank mix testing looks at the effects on a drug formulation when it is diluted or re-suspended with various levels of water hardness, as opposed to only de-ionized water. Some types of water hardness can affect the stability of a formulation, cause phase separation and decrease the time that a solid formulation stays suspended in liquid. Understanding these effects allows a formulator to evaluate the need to revise the formulation composition by adding an adjuvant or other ingredient to reduce potential negative impacts. It is beneficial to perform these water hardness tank mix evaluations at varying temperatures and time points.
Tank mix compatibility testing also encompasses combining drug formulation samples with other frequently combined ingredients or formulations based upon the route of administration. This type of situation may occur in a setting where drug formulations are combined in an IV bag, put together in liquid suspension or made into a solution. Tank mix testing looks at the stability of the formulation in the presence of another formulation and physical form changes that could affect the performance or application of the active ingredient, such as increased precipitation, crystal formation, phase separation, etc.
Hamilton's automated solutions can aid in tank mix testing by providing software that allows scientists to easily set up the different combinations of formulation and water hardness types, as well as the combination of multiple formulations inside the same sample vessel. Once the experiment is designed, Hamilton’s automated liquid handler can automate the pipetting of these components into specified vessel types (i.e., tubes, wells of an SBS plate, etc.), where the samples can be mixed and stored at various temperatures for a specified amount of time. The automated liquid handler can take aliquots of the mixtures at desired time intervals for further quantitative analysis, or qualitative data can be obtained by capturing images of the formulation mixes by utilizing the CCD camera or tube gripper and automated imaging station.
The image below shows four Hamilton prepared tank mixes of a drug formulation stability in four types of water: A = DI water; B = 1026 ppm water, C = 760 ppm water; and D = 342 ppm water. This qualitative data shows the impacts of water hardness on the performance stability of a drug's formulation after a certain amount of time.
The image below shows two formulation mixtures testing two trial formulations for Drug A and a market-available formulation for Drug B, which are considered commonly combined drugs. Each of the two tank mixes had images captured initially with normal lighting after being mixed at Time 0, after a specified amount of time (Time 1) and after a specified amount of time with polarized light (Time 1PL). The image of the three vials on the left shows Drug A1 and Drug B interact and form crystals in situ. The image of the right three vials shows Drug A2 and Drug B with no signs of crystal formation, and therefore the tank mix is considered compatible.