Flavour technology in pharmaceuticals

Palatability assumes crucial role in patient compliance and hence selection of brands, say Dr Gupta and Aziz Ahmed

Recalling a decade back when I had developed my first product, the CEO of the company sent across a communication that this is the first product of the company that ’tastes like medicine! ‘I got bemused by the reaction whether that was to appreciate me or otherwise. As a proletarian, I had a notion that ‘a medicine should taste like a medicine’, perhaps it was the opposite that was required. Palatability is a big issue in the pharmaceuticals as it affects the patient compliance; it’s still a bigger issue in the OTC segment as it affects consumer’s selection of the brand.

This article is aimed at providing brisk information to the product development scientists about fundamental and applied aspects of flavour technology.

What is Flavour?

Flavour is a sensation produced by a material taken in the mouth. Perhaps, mainly the senses of taste and smell perceived it, it’s also perceived by the tactile and temperature receptors in the mouth.

Taste: There are four basic tastes ie. Bitter, Sweet, Sour and Salty that human beings perceive through specific areas on the tongue. When any material is taken in the mouth taste molecules get weakly absorbed in the taste-areas where upon reaction with the taste receptors they change/ disrupt molecular geography of receptor, and the exchange of ions across the surface; henceforth, a nerve impulse is generated transmitting a taste signal to the brain. Any material’s ability to induce this effect depends on its chemical structure, and hence, any chance in its chemistry results in the loss or change in the taste eg. saccharin is a sweet but on alkylation it becomes tasteless.

Mechanism of Taste Transduction: The taste transduction mainly takes place through two ways: Bitter and Sweet involves G Protein coupled receptors while Salty and Sour are mediated via ion channel. The taste specific G Protein gustducin, which is analogous to the transudin, a protein of the visual system, present alongwith the later in the taste buds gets activated and dissociated into alpha, beta and gamma subunits. The alpha subunit of this protein activates the intracellular phosphodiesterase leading into decreased CAMP levels. The reduced CAMP level activates ion-channels resulting in a change in the taste cell potential. In a similar fashion, beta and gamma subunits activate Phospholipase C, which has the ability to generate messengers IP3 and DAG. IP3 mobilises intracellular stores of calcium and thereby modulating the taste cell membrane potential. The non-gustducin mediating substance navigate across the taste cell membrane and directly modify down-stream signal, hence, any compound blocking activation of taste receptor or down-stream signaling protein, affects the perception of taste.

i) Sweetness: Out of the several theories that exist for sweet taste the most popular one is AH, B theory, which states that compounds giving a sweet flavour have an electro negative atom (eg Oxygen or Nitrogen). The AH could be a hydroxyl group, amine group or a methine group. A second electronegative atom B (eg oxygen or nitrogen) is also found in the molecule. AH, B unit found at the taste receptor react with the AH, B system of sweet compounds by forming simultaneous hydrogen bonds, which generates the sweet taste signal. This property is molecular weight dependent and as the molecular weight increase the sweetness deceases eg carbohydrates, which are sweeter when at low molecular weight.

ii) Bitterness: For any molecule to induce a better taste signal it requires having at least one polar group and a hydrophobic group. Perhaps, hydrogen bonding proton and electronegative atom may also be found in it, the discrimination between bitter and sweet taste is based on the orientation of the receptor sites. Many bitter compounds are inorganic salts, amino acids, alkaloids and glycosides. Undesirable bitterness of peptides is estimated on the basis of overall hydrophobicity of amino side chains.

Mean hydrophobicity value (Q) is used to predict whether or not a molecule will taste bitter. The ability of a protein to engage in hydrophobic interaction is related to the sum of the individual hydrophobic contribution of the non-polar amino acid side chains.

Q=†DG N Q Where, N=Total number of amino acid side chains. DG = Free energy associated with protein unfolding. If Q ,5436 KJ mol -1, Peptide will not taste bitter, but if Q .5855 KJ mol -1 the Peptide is liable to be bitter.

For lipid derivatives and sugars, the ratio of carbon atom to OH group influences whether the molecule will taste sweet or bitter. If the ratio (R) is 1.00 to 1.99 then it tastes sweet and if (R) is 2.00 to 6.99, bitter.

iii) Saltiness: Saltiness basically exists because of cations, which is affected by the presence of anions. The anions may inhibit the taste of cations or may induce their own taste eg Sodium laureate tastes soapy due to anion. The salty compounds have ionic diameter less than 6.5 A0 and as this increases the bitterness is increased.

iv) Sourness: Sourness is basically expressed due to hydrogen ions. Its degree and type depends on the nature of the acid group, pH, titrable acidity, buffering effects and presence of other compounds such as sugars.

v) Other Taste Responses: Pungency and cooling are extra allied taste sensations. Pungency, with is hot, sharp, stinging sensation typically associated with chili powder, black pepper and ginger. Cooling is associated with mint like flavors particularly menthol, which because of its local anesthetic action actually blocks the hot receptors in the mouth. Other mechanisms by which cooling sensation is produced may involve compounds that have endothermic heat of solution e.g. glucose.

Dr V B Gupta*, director, BRNCP, Mandsaur & Aziz Ahmed, LMCST, Jodhpur