Maintaining product quality, ensuring safety and efficacy, and meeting regulatory requirements are fundamental to pharmaceutical development and manufacturing. While much attention is given to chemical composition and biological activity, physical properties such as colour, density and viscosity also play a key role in product quality and patient safety. This article focuses on colour since it is a critical quality attribute (CQA) in pharmaceuticals - providing essential information on product identity, batch-to-batch consistency, and stability across dosage forms.
Key physical properties for determining pharmaceutical quality
The table below provides an overview of some physical properties that are key to pharmaceutical quality, along with the corresponding compendial references, specifically from the United States Pharmacopeia (USP) and the European Pharmacopoeia (Ph. Eur.).
| Physical Property | Relevance to Pharmaceutical Industry | USP | Ph. Eur. |
|---|---|---|---|
Colour | Immediate visual indicator of a product’s identity, stability, and quality. Also critical in ensuring compliance with pharmacopeial standards. | <631> Colour and Achromicity
<1061> Colour-Instrumental Measurement | 2.2.2 Degree of coloration of liquids |
Viscosity | Consistent viscosity in liquid and semi-solid preparations ensures uniform drug potency across all manufacturing stages. | <911> Viscosity – Capillary Methods
<912> Viscosity – Rotational Methods | 2.2.9 Capillary Viscosity Method
2.2.10 Viscosity – Rotating Viscometer Method |
Density/specific gravity | Density influences drug formulation, stability and bioavailability. Thus density measurements provide insights into the physical properties of raw materials, intermediates and finished products. | <841> Specific Gravity | 2.2.5 Relative Density |
Refractive Index | Every substance has a characteristic Refractive Index under specific conditions. In pharmaceuticals, refractive index measurement is essential for substance identification, quality control, and purity assessment in formulations. | <831> Refractive Index | 2.2.6 Refractive Index |
Conductivity | Conductivity is used for monitoring water purity, formulation monitoring and validating cleaning processes | <644> Conductivity of Solutions
<645> Water Conductivity | 2.2.38 Conductivity |
The role of colour in pharmaceutical products
Liquid Dosage Forms: Colour is commonly measured in oral solutions, syrups, injections, and ophthalmic products to detect impurities, degradation, contamination or instability. USP <631> Colour and Achromicity and Ph. Eur. 2.2.2 Degree of Coloration of Liquids provide standard procedures for visual comparison or instrumental colorimetry against colour reference standards.
Solid Dosage Forms: Colour in tablets, capsules, and powders is critical for product identification, differentiation of dosage strengths, brand recognition, and patient compliance. It's also a key tool in detecting coating defects, intra-batch variability, as well as degradation, and is often evaluated using reflectance spectrophotometry.
Semi-Solid Forms: In creams, gels, and ointments, colour is monitored to ensure uniform appearance, detect oxidation or microbial growth, and maintain consumer acceptability for consistency and stability. Visual and instrumental methods are both used, depending on product criticality.
Colour reference standards and compendial methods for liquid pharmaceuticals
International pharmacopeias, including the United States Pharmacopeia (USP) and European Pharmacopoeia (Ph. Eur.) International pharmacopeias, including the United States Pharmacopeia (USP) and European Pharmacopoeia (Ph. Eur.), provide defined methods and specifications for colour measurement, using colour reference standards for visual comparison.
In USP <631> visual comparison method, the sample is visually compared with colour reference standards in clear containers under controlled lighting. The standards consist of a series of 15 matching fluids (A-T) derived from three primary solutions prepared from known amounts of cobaltous chloride (CoCl2), ferric chloride (FeCl3), and cupric sulfate (CuSO4), mixed with water.
In Ph. Eur. 2.2.2 visual methods, the sample and colour standards are compared in diffused daylight, viewing either horizontally or vertically against a white background. There are 37 colour standard solutions (B1-B9, BY1-BY7, Y1-Y7, GY1-GY7 and R1-R7), which are prepared from three primary colour standard solutions (yellow, red and blue) mixed with hydrochloric acid and water to make five standard colour solutions – B (brown), BY (brownish-yellow), Y (yellow), GY (greenish-yellow) and R (red). These five standard colour solutions are further diluted with hydrochloric acid to make the 37 reference liquid colour standards that are used for visual comparison with drug solutions.
USP <631>, USP <1061> and Ph. Eur. 2.2.2 include an instrumental method for colour measurement that is based on a CIE L*a*b* determination devised by the International Commission on Illumination (CIE). The use of a spectrophotometer or colorimeter provides more objective data than visual comparison by individuals. However, the methods still require the use of colour reference standards to ensure accuracy of data.
Stay up to date with LGC Standards’ USP and Ph. Eur. colour standards
Help your laboratory comply with current regulatory demands by choosing LGC Standards' USP and Ph. Eur. colour standards that ensure accuracy, consistency, and full traceability - so you can test with confidence and meet pharmacopoeial requirements every time.
Other physical property standards, reagents and volumetric solutions available from LGC Standards include:
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