Taste Masking - a complex challenge

Taste?is a patient-centric topic, but also has broader cultural considerations.?Foods that taste good?to one?person?may?not automatically please others as?we have quite some regional differences to take into account.?Is the same?also true for medicines??Absolutely! I still remember my mother telling me that?a?medicine tasted?so bad because it works. Frankly,?I preferred the sweet tasting cough syrup at that time.?This topic becomes even more difficult?when it comes to animals –?trying to?convince a cat to take a medicine she does not like: "Mission impossible". The acceptance of a flavor is only a part of the game, the other is whether the flavor “works” with the API and excipients in the formulation - not to forget the potential impact of the flavor quality. So yes, taste and taste masking is a complex challenge.

But now I would like to refer to the excellent article by David Tisi from Senopsys which we published earlier this week on pharmaexcipients "Taste Masking Challenge of 150 APIs"

It is widely recognized that many Active Pharmaceutical Ingredients (APIs) are bitter, some extremely so. But bitterness is not the only challenge in creating palatable, patient-accepted drug products.

What are some of the other aversive sensory attributes?

To answer this question,?Senopsys?compiled data from 150 API taste assessment studies and the results are summarized in the pie chart above and below (excluding over-the-counter drugs).

For almost 70% the APIs (mostly new chemical entities or “NCE”), the primary taste masking challenge was?bitterness. Of the other basic tastes, a few were?sour?(3%) or?salty?(4%). None were found to be sweet.

Aversive odors (“aromatics”) were the primary sensory challenge for approximately 7% of APIs. Some descriptors of these malodors included “phenolic” (like Band-Aids), “sulfidy” (overcooked cruciferous vegetables), “oxidized oil” (like old paint), and “solventy” (e.g., acetone, or ether-like).

The primary challenge for another 4% of the APIs was a strong intensity trigeminal irritancy (these included oral or throat burning, numbing, and tongue stinging). Finally, 16% of APIs were fundamentally tasteless, but their challenge was driven by the negative sensory attributes of the?excipient?system, e.g., surfactants, co-solvents, and solubilizers.

Most APIs have multiple aversive attributes!

There’s a general misconception that most APIs have a single aversive attribute but that’s not our experience.?The pie chart above shows the aversive attributes that make up the secondary taste masking challenge of those same 150 APIs.?Unlike the bitter-weighted primary challenge, these secondary challenges are heavily represented by aromatics (malodor) followed by trigeminal irritancy, sour and salty basic tastes, “other” (e.g., aversive mouthfeels and textures), and bitter basic taste. While these are results from Senopsys studies and may not be representative of all APIs, it’s safe to say palatability issues go beyond bitterness!

Why is it important to identify the aversive sensory attributes?

Taste, smell, and irritation represent different perception pathways and importantly, the approach for dealing with each is fundamentally different. “Taste” refers to those sensations – sweet, sour, salty, and bitter – perceived through stimulation of the receptor cells located in the taste buds on the tongue and oral cavity. Taste issues are addressed via balancing their intensity with other basic tastes to minimize the perception of each individually.

Negative aromas may be minimized through the judicious incorporation of commercial “flavors” which are mixtures of aroma chemicals that are perceived through the sense of smell (olfaction) – e.g., orange, strawberry, mint. These have no effect in reducing bitterness or the other so called basic tastes – sweet, sour, and salty. Similarly, compounds such as capsicum (red pepper), piperine (black pepper) and many APIs produce a burning sensation when thermoreceptors connected to the trigeminal nerve are activated – this is known as chemisthetic perception. The addition of tastants or odorants (flavors) has no effect on burning because they are fundamentally different modalities.?This is analogous to how aspirin would not be administered to treat a bacterial infection.

So how are the critical aversive sensory attributes measured to diagnose the problem?

Interested to learn more? Continue the article here and / or here more from David Tisi during the upcoming ExciPerience!