Integrating tristimulus colorimetry into pharmaceutical development for color selection and physical appearance control: A quality-by-design approach

摘要

The color of pharmaceutical dosage forms can be an important aspect of product branding and patient compliance with a dosing regimen. During the development of drug products, it is important to understand the stability of not only the active pharmaceutical ingredient but also the color and appearance of the tablet or capsule. Currently, the most common method to ensure color stability is to conduct a visual test throughout a stability study. This visual test is subjective and can be expensive, especially if there is a failure late in development or after marketing approval. This work describes a series of studies using accelerated conditions (i.e., heat, humidity, and light) and logistic regression analyses that have been developed to determine the relative stability ranking of multiple color coatings early in development to provide an increased probability of technical success on long-term stability studies and to avoid coatings whose visual appearance may change over time. Once this relative stability ranking has been established, the stability advantages can be assessed versus any manufacturing/processing liabilities of the selected coating in order to make a data-driven decision around coating selection. This work reviews the basic fundamentals of colorimetry, followed by the description of a consistent experimental approach to correlate a visual rating with an instrumental measurement (e.g., dE from a colorimeter) to remove the subjectivity from the assessment. This approach represents a novel strategy for establishing a probabilized correlation between the quantitative instrumental color measurement and the visual rating of the same color change.