Methods of Analysis Used in Taste Masking

Sensory analysis is defined as the “scientific discipline used to evoke, measure, analyze, and interpret those responses to products that are perceived by the senses of sight, smell, touch, taste, and hearing”(1).
By definition, sensory analysis methods entail the use of human subjects (i.e., in-vivo methods). These methods are most commonly employed to guide the development of palatable formulations.
There are two broad classes of sensory analysis methods:

• Analytical methods – used to measure the attributes of products and guide formulation development.
• Affective methods – used to measure human response to products and select the most liked or preferred formulation.

There are also in-vitro models that have been advanced for studying the taste attributes of new chemical entities (NCEs) in preclinical research. As these models do not use human subjects they are not considered sensory analysis methods per se.

Analytical methods are used to measure the attributes of products.
The two most commonly used analytical techniques in pharmaceutical development are descriptive sensory analysis using trained subjects and discrimination testing using trained or untrained subjects.
The descriptive methods are used to identify and quantify the sensory attributes of products – basic taste, aroma, mouthfeel, and texture. These are most commonly employed to quantify the taste challenge and guide the development of palatable, taste-masked formulations.
There are several descriptive sensory analysis methods – Senopsys uses Flavor Profile, an internationally recognized, open-source (i.e., non-proprietary) method of sensory analysis. Flavor Profile uses trained adult assessors, known as “panelists” to:

1. Identify the perceived attributes – taste, aroma, mouthfeel and texture.
2. Rate the intensity of each perceived attribute using a measurement scale that is established with chemical reference standards.
The output is analogous to a chromatogram, wherein each peak represents a separately identified sensory attribute and the peak height/area corresponds to perceived strength or intensity of each attribute.

Affective tests are used to measure human response to products.
The most commonly used affective tests are hedonics (liking) or preference and these always use untrained respondents, ideally the target patient population. Affective tests can be conducted on either an absolute or relative basis. Liking is measured on an absolute basis whereas preference is always a relative measure. As pre-verbal children and infants are unable to express their preferences clearly, other techniques must be employed. These include caregiver interview questionnaires, facial expression interpretation or Likert-type pictorial hedonic scales.

Due to the unique challenges surrounding drug development, there are a variety of analysis methods that can be used to answer different taste questions along the continuum from pre-clinical assessment to formulation development to manufacture of clinical trial materials and commercial products.
In-vitro models are being studied to gain early insight into potential aversive attributes of drug actives in pre-clinical research. However, there is limited published research that shows a relationship between preclinical tests of NCEs and human response. As such these models are currently of limited utility in predicting taste issues or guiding the development of palatable formulations.
When first-in-human clinical studies indicate potential palatability issues, or if these remain unknown, descriptive sensory analysis methods are commonly used to guide formulation development. For example, to:

• Identify the aversive sensory attributes
• Quantify the taste masking challenge
• Measure reduction in aversive taste attributes
• Develop palatable, age-appropriate formulations

For pediatric drug products, the regulatory agencies are increasingly requiring manufacturers to conduct palatability studies in the target patient population to demonstrate ease of dose administration. Affective tests are designed and executed in a clinical setting to measure degree-of-liking or preference as indirect measures of “palatability” or “acceptability.” The design of the test instrument is dependent upon the age of the children as described above.
Finally, in-vitro techniques such as the “electronic tongue” (“e-tongue”) can also be used to measure differences from an established “gold standard.” In the absence of correlation to human sensory response data, these techniques are of limited utility in development environments or selecting formulations and are most commonly used in quality control.

There are many sensory analysis tools available to formulation scientists to help them develop palatable, taste-masked drug products. No single method is amenable to addressing the differing needs along the development pathway. The fundamental choice depends upon whether you want to measure the product’s attributes (analytical methods) or patient response to the product (affective methods). Hopefully this post will help you make the right choice!

(1) Stone, H and Sidel, JL. 1993. Sensory Evaluation Practices. 2nd ed. Academic Press: San Diego.

Prepared by Senopsys LLC by David Tisi — All Rights Reserved

David Tisi is the Technical Director of Senopsys LLC, a specialty services firm dedicated to the development of palatable drug products. He has 15 years of experience in taste assessment and taste masking of investigational and approved drugs for children and adults, leveraging his background in sensory science and food chemistry. He can be reached at [email protected]