Can Color Analysis Be Used for Both Liquid and Solid Pharmaceutical QA/QC?

In pharmaceutical manufacturing, the color of a drug product is important to analyze for QA/QC purposes. Not only is it necessary to minimize batch-to-batch variations for aesthetic purposes, but changes to the color of a product can have implications for the quality of the products. Specifically, variations from the anticipated color could indicate impurities are present in the product or that the material has degraded.^1–3 This is particularly important for materials which are easily decomposed, including light, moisture, and oxygen/air-sensitive substances.⁴ Color analysis can be a quick and useful tool for assessing the overall quality of a given product prior to further downstream processing.

Through UV-Visible spectroscopy, the analysis can be made more rigorous, free from person-to-person bias, allowing for a more accurate measurement of color. However, can color analysis be applied to both solid and liquid samples?

To answer this question, the following samples were analyzed using UV-Visible spectroscopic techniques: a set of USP color-matching solutions, daytime cough syrup, a night-time cough syrup, and a set of four different antacid tablets of different colors. In these experiments, all solid samples were measured using reflection techniques while liquid samples were measured using transmission techniques, including both percent transmission (%T) and absorption spectra.

According to USP <631>, color-matching solutions are to be used as a comparison point against the produced liquid product to ensure the product matches the expected color.⁵ As many liquid-based pharmaceutical products are yellow in hue, the USP monograph includes a procedure for making a set of standard solutions of varying yellow. EP has a different procedure outlined for making color standards and includes a wider range of colors, including brown, green and blue, among others.⁶

USP <631> specifically refers to color analysis procedures for liquids; however, color analysis can be performed using solid samples as well, according to USP <1061>.^5,7 For pharmaceutical analysis, the color of a solid drug product can also have implications on the quality of the material; however, it can also be used to indicate the dosage of a given product as well as comply with a company’s branding or marketing needs.⁸ For solid materials, measurements in reflection geometry are appropriate as it is difficult to pass light through a solid material without scattering effects.

The experiments described above and resulting analysis are further discussed in an application note about color analysis and its implementation for both solid and liquid samples measured using UV-Vis spectrophotometers. Read about the materials and instruments used, the parameters, and the results in Color analysis for pharmaceutical products using UV-Visible absorption techniques.

The experiments conducted will show that color analysis can be an effective and quick method for QA/QC in pharmaceutical manufacturing. The application note illustrates how  color analysis can be performed using UV-Visible Spectrophotometers to carefully determine a material’s color without person-to-person variations, allowing for a quantitative analysis of a produced pharmaceutical. Additionally, these measurements demonstrate the ability to analyze both liquid and solid samples following USP color analysis procedures.

Resources, Notes, and References:

• Application note: Color analysis for pharmaceutical products using UV-Visible absorption techniques.
• For Research Use Only. Not for use in diagnostic procedures.

References

1. Zhou, L.; Vogt, F. G.; Overstreet, P. -A.; Dougherty, J. T.; Clawson, J. S.; Kord, A. S., A Systematic Method Development Strategy for Quantitative Color Measurement in Drug Substances, Starting Materials, and Synthetic Intermediates, J. Pharm. Innov., 2011, 6, 217 – 231.

2. Yamazaki, N.; Taya, K.; Shimokawa, K.-I., Ishii, F., The Most Appropriate Storage Method in Unit-Dose Package and Correlation between Color Change and Decomposition Rate of Aspirin Tablets, Int. J. Pharm., 2010, 396, 105 – 110.

3. Oram, P. D.; Strine, J., Color Measurement of a Solid Active Pharmaceutical Ingredient as an Aid to Identifying Key Process Parameters, J. Pharm. Biomed. Anal., 2006, 40, 1021 – 1024.

4. Berberich, J., Dee, K.-H., Hayauchi, Y., Pörtner, C., A New Method to Determine Discoloration Kinetics of Uncoated White Tablets Occurring During Stability Testing – An Application of Instrumental Color Measurements in the Development Pharmaceutics, Int. J. Pharm., 2002, 234, 55 – 66.

5. United States Pharmacopeia and National Formulary. <631> Color and Achromicity. In: USP–NF. Rockville, MD: USP.

6. European Pharmacopoeia. 2.2.2. Degree of Coloration of Liquids. In: European Pharmacopoeia. Strasbourg, France: European Pharmacopoeia.

7. United States Pharmacopeia and National Formulary. <1061> Color – Instrumental Measurement. In: USP–NF. Rockville, MD: USP

8. Hetrick, E. M.; Vannoy, J.; Montgomery, L. L.; Pack, B. W., Integrating Tristimulus Colorimetry into Pharmaceutical Development for Color Selection and Physical Appearance Control: A Quality-by-Design Approach, J. Pharm. Sci., 2013, 102, 2608 – 2621.