Taste Masking Challenge of Solubility Enhancing Excipients

Taste Masking Challenge of Solubility Enhancing Excipients – A Case Study

An estimated 80% of new drug actives are classified as poorly soluble. There are a number of approaches for enhancing solubility – alternative salt forms, particle size reduction and solubility-enhancing excipients, among others. Like APIs, many excipients are known to be bitter or have other aversive sensory attributes including aromatic off-notes (malodor) and trigeminal irritation (e.g., tongue sting and mouth/throat burn). In some cases, the taste masking challenge of the excipient system can be greater than for the API itself.

Approach

To ensure development of a palatable, patient-accepted drug product, the taste masking challenge of the API and candidate solubility-enhancing excipients was determined.
First, a sensory analysis of the neat API was conducted by a trained sensory panel using the Flavor Profile method (Keane 1991), following Good Clinical Practice. The results indicated the API was fundamentally “bland” tasting.
Then the flavor quality of five classes of solubility enhancers was assessed. To do so, minimum and maximum usage levels were established and, samples from multiple suppliers were sourced.

Results

Shown below are the time/intensity profiles for the “cleanest” source across the five classes of solubility enhancing excipients. For each, the intensity of the predominant aversive sensory attribute is plotted at its maximum estimated usage level.
A slight intensity (1) on the Flavor Profile scale is the intensity at which an untrained consumer/patient can describe a perceived attribute, e.g., tastes bitter. Therefore, to ensure palatability, the intensity of the aversive attributes should remain below a slight intensity (<1). Empirical color-coded decision boundaries are shown to facilitate interpretation.
As shown, the five classes of solubility enhancing excipients varied in terms of their sensory attributes – most notably bitter basic taste, aromatic off-notes, trigeminal irritation (burning) and mouthfeel effects (oily/waxy).

A common misconception among formulators is that monographed excipients from different suppliers are “interchangeable.” While this may be the case for some functional properties, it is seldom the case for flavor quality.
To illustrate, the aversive sensory attributes of a NF grade tocopherol surfactant from two suppliers are shown below. The material from Manufacturer #1 had a “cleaner” Flavor Profile with lower bitterness, mouthfeels (burning and waxy) and absence of malodor (burnt hair). Use of this material will result in a more palatable formulation than from Manufacturer #2.

Conclusions

In summary, it’s important to consider sensory properties when selecting excipients. Ideal candidates should be chosen to simultaneously optimize for functionality (e.g., solubility) as well as palatability.

Have a look at our other Taste Masking Article:

The Taste of 101 API’s summarized

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]