Using an Electronic Tongue to Optimize Taste-Masking in a Lyophilized Orally Disintegrating Tablet Formulation
Using an Electronic Tongue to Optimize Taste-Masking in a Lyophilized Orally Disintegrating Tablet Formulation
Owen J. Murray,* Wenbin Dang, and David Bergstrom
Pharmaceutical Technology
Making orally disintegrating tablets (ODTs) and their
active pharmaceutical ingredients (APIs) palatable
is one of the most significant technical obstacles to
?patient friendly? formulations.
This is particularly important for lyophilized tablets, which
disintegrate nearly instantaneously when placed on the tongue.
The formulation?s organoleptic properties?taste, mouth-feel
and appearance?are of considerable importance in differentiating
products in the market and can ultimately determine
the success, or otherwise, of a product.
Pharmaceutical taste-assessment typically requires a large,
trained taste panel, and sophisticated interpretation. The tests
may require the same health safeguards as a clinical trial. All
told, a properly conducted taste test adds time and money to
the development process.
Here, we describe an objective, quantitative approach to ODT
taste analysis and taste masking, using an electronic sensor array,
the ?e-tongue.?
Some of the characteristics that make ODTs valuable for drug
delivery also pose special challenges to palatability. The tablets
are very porous, which allows water to penetrate instantly, dissolving
the matrix and releasing the active pharmaceutical ingredient.
Thus, patients may take ODTs without water, and without
the compliance issues often associated with swallowing solid
tablets whole (especially when the patients are very young or
very old).As a variety of ODT approaches?lightly compressed
tablets, compression-molded tablets, and films?join moretraditional
liquid and chewable preparations, effective taste-optimization
becomes more crucial to product success.
Taste is a survival mechanism, alerting us to potentially harmful
or potentially nutritious substances.We process taste at three
levels: the receptor level, the circuit level, and the perceptual level.
At the receptor level are approximately 10,000 chemoreceptors
or taste buds, residing primarily on the tongue, with some
delocalized receptors at the back of the throat. These receptors
fall into five primary categories: bitter, sour, umani, salt, and
sweet, with grouped receptors dissipated over the surface of the
tongue for each stimulus (see Figure 1 and Table I).
Sweet signals carbohydrates or certain amino acids. Sour
characterizes vitamins. Salt detects needed minerals.Umani indicates
protein and amino acids. In general,we experience these
tastes as pleasant. Bitter sensation, however, is often unpleasant,
suggesting alkaline water, alkaloid poisons, and spoiled
foods. APIs, of course, usually fit into the bitter category.
Chemoreceptors for taste and olfaction (smell) respond to
chemicals in an aqueous environment. Chemicals dissolved in
saliva excite the taste receptors of the mouth, and airborne chemicals
dissolved in epithelial mucus excite the olfactory receptors
of the nose. The senses are complementary, with smell and taste
working together to respond to, and more narrowly define, the
same stimuli.
Taste depends on physiological and psychological factors.
Physiological properties such as temperature and texture, clearly
affect the perception of taste (consider the limited appeal of a
cold cup of coffee). Human taste also appears to change with
age. Many children dislike fresh vegetables, yet grow to enjoy
them in adult life. Psychological factors can also influence taste
perception: a childhood memory of badly formulated cough
medicine can significantly modify taste perception of a modern
formulation. Such factors underscore the role of taste in
manufacturing a product that achieves patient compliance.
Culture influences perceived palatability.Market research has
revealed standard combinations of specific sweeteners with relevant
flavors and colors, which may vary by country and target
market.National favorites include ?green tea? in Japan,?bubblegum?
in the United States,?citrus? notes in Europe, and ?licorice?
in Scandinavia. A bubblegum or cherry flavor married with a
red color and high intensity sweetener may suit a US pediatric
market, while a less intense sweetener may be more appropriate
for Japan. Similarly, a mint flavor coupled to a white unit
may be a more traditional approach for an adult market.
Regardless of the flavor system used,
the challenge is how to deliver unpleasant
compounds (APIs) while maintaining
patient acceptability, efficacy, and
Several formulation approaches may
mask an unpleasant-tasting API. In tests
of our proprietary lyophilized orally disintegrating
tablet (the Zydis formulation
from Cardinal Health, Somerset, NJ), we
have successfully used coating of the drug
substance, complexation (as with ionexchange
resins) to remove the API from
solution, lecithins or cyclodextrins, and
pH modification (to a value that renders
the API insoluble), along with more traditional
sweeteners, colors, and flavors.
Clearly, any complexation or insolubilization
technique that inhibits interaction
between the drug and the taste buds
may also affect API dissolution and absorption
profiles. It is thus critical to develop
ODT performance and taste formulation
Because pharmaceutical taste-assessment
can demand large panels and elaborate
analysis and raise safety and scheduling
concerns, a full taste program can
be time-consuming and expensive.Alternatively,
the ?taste study?may be reduced
to an informal gathering of executives,
who reach consensus on the best formulation
without considering statistical significance
or protocol. Data derived by such
a method is highly subjective, limited, and
potentially biased.
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