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Physical Appearance Determination of a Drug Substance

Physical Appearance Determination of a Drug Substance Utilizing a Commercially Available Color Guide
by Jennifer Alligood, Kimberly Lupo, Joe Cobb, Lauren McNeil, Ashley Dunning, Lauren Brock, Ken Jones, Credle Harris, Marjorie Misiura, David Nelson, Kym Rispress

To develop a robust method to determine the physical color appearance of drug substance X that eliminates the subjective human bias for color selection.

General Background
Physical appearance testing can be the most subjective but important tests performed on drug substances. The polymorphous form can provide information regarding the solid state of the material. The color can be an indication of purity and a means to identify contamination that occurred during the synthesis process. Typical testing involves viewing the material against a white background under specified lighting and reporting the color and form. Due to human bias observed during physical appearance testing of drug substance X, a commercially available color guide was utilized to develop a robust method to determine the physical appearance of said material.


Active Pharmaceutical Ingredient (API) X, Form A, Micronized, Supplied by Client
Active Pharmaceutical Ingredient (API) X, Form B, Non-Micronized, Supplied by Client
Active Pharmaceutical Ingredient (API) X, Form B, Micronized, Supplied by Client
Pantone® Formula Guide, Solid Uncoated, Product Code GP1201
White Computer Paper

Analytical Equipment:
Light Booth, Byko-Spectra, Part No. CG-6050
Olympus Model C2020Z Digital Camera

Visual Method
The following data were collected on several different lots and type of API X by three analysts using the visual method. The visual method consisted of viewing approximately 50 mg of API X placed on a white sheet of paper under laboratory lighting. The color of the API was recorded by each analyst without the knowledge of what the other analyst had recorded. There was some variability within each sample tested.

Table 1 – Visual Method Results

Pantone Formula Guide
The Pantone Formula Guide (Solid uncoated) is a commercially available compilation of color swatches. Each color swatch contains seven color shades represented by a numerical code (i.e. Color shade:4685U, Color swatch 55.5U). Refer to Figure 1 for a picture representation of the terms color shade and color shade. The color guide includes hundreds of color shades. Therefore, it was desirable to eliminate the color shades from the guide that was not needed for testing purposes but would give the analyst realistic color standards to compare the sample to.

Figure 1. Description of Terms Used

Table 2 – Initial Pantone® Method Results

All of the samples that were tested per the visual method were compared to the all of color swatches contained in the Pantone® Formula Guide Solid Uncoated by two analysts. Two additional samples were also compared. The results shown below are reported as a color shade number followed by a color swatch code in parenthesis.