A variety of pharmacologically active substances orally administrated are proved to be quite effective in treating diseases. However, their undesirable organoleptic sensations (e.g., aversive taste and/or odor) always severely compromise their treatment efficiency especially in pediatrics owing to the low patient acceptability. Therefore, the developments of taste masking techniques are of great importance in improving the patient compliance and then their curative efficacies in clinic.

In recent years, diverse of taste masking techniques have been widely utilized to mask the unpleasant taste of chemical drugs at three levels in clinic. First, in formulation level, diverse sweeteners, flavors, and bitter blockers were used alone or in combination to mask such drugs’ taste and/or odor. For example, 0.8% aspartame, a high-potency sweetener, could significantly reduce the bitter taste of 25% acetaminophen in solution [1]. The higher taste-masking efficiency could be achieved by the combination of sweeteners and flavors (for example, the mixture of sodium saccharin and some flavors was used to conceal the bitterness of ibuprofen formulated as syrup with pyridoxine HCl) [1]. This may be owing to that different sweeteners and flavors target different types of taste receptors, and thus, more G proteins are activated to transfer more nerve signals to sweetness-perceived areas in the brain [2]. As for bitter blockers, due to possessing sufficiently strong bitter-masking capability, they are often used alone to inhibit the bitterness of chemical drugs (e.g., γ-amino butyric acid could effectively suppress the unpleasant taste of catechin) [3].

Second, in particle level, polymer film-coating and lipid barrier systems can impart a physical barrier onto the surface of bitter components to prevent the contacting of drugs and taste receptors in the mouth. In the polymer film-coating, pH-responsive polymers are often used. For example, mequindox-loaded mesoporous silica nanoparticles was coated a kind of pH-sensitive polymer (Fe-4,4'-bipyridine complex) by virtue of metal-organic coordination cross-linking [4], which showed a rapid drug release at pH 1.0 but a delayed release at pH 6.6. Namely, the entrapped drug could not rapidly diffuse from the surrounding polymer to be perceived its bitter sensation in the oral cavity. Similar results could be also found in paracetamol-entrapped polymers [5]. To further prevent such drugs from releasing in the mouth and eradicate their bitterness, a double coating layer consisting of saliva-insoluble Eudragit RS30 as inner layer and water-permeable Eudragit RL30D as outer layer was used to coat cetirizine HCl [6]. Moreover, to acquire better coating effect, microencapsulation was applied to enwrap such drugs (e.g., prednisolone microparticles based on  Eudragit E PO or E 100 efficiently masked the drug’s taste and completely and rapidly released drug at pH=1.2) [7]. One more advantage for microencapsulation is that the coating layer of microencapsulated taste-masking particles could remain intact during being compacted into orally disintegrating tablets, as well [8]. In lipid barrier systems, various lipids (e.g., glyceryl monostearate, waxes) and solid lipid nanoparticles were utilized as coating layer or drug carriers to mask the unpleasant taste of these drugs with a solvent-free process [6, 9, 10].

Third, in molecular level, charged polymers, β-cyclodextrin, and ion-exchange resins have been used to complex drug molecules with the purpose of masking their taste. For example, cationic Eudragit EPO was used to complex ibuprofen through the process of hot-melt extrusion [11]. The achieved bitterness suppression of ibuprofen was owing to the formation of hydrogen bonding between ibuprofen as a hydrogen donor and cationic functional tertiary amino of Eudragit EPO as a hydrogen bonding acceptor. In other cases, drug molecules (e.g., cetrazine, diltiazem hydrochloride, dextromethorphan hydrobromide, and tramadol) were enwrapped into the inner cavity of cyclodextrin or adsorbed by charged resins to acquire the taste-masking effect [12-15].

However, the application of these taste masking techniques in traditional Chinese medicine (TCM) is relatively premature, though the taste and/or odor of most TCM are always unpleasant or even repulsive. The types of TCM include bioactive single ingredients, effective fractions, single Chinese herbs, and compound preparations. Except the single ingredients, the left TCM sources are all multi-component complicated systems, in which both the bitter components and the structure-activity relationship are generally unclear. Thus, it is much difficult to find out a kind of tailor-made taste masking technique to cover the unpleasant taste of such systems, and there are relatively limited researches paying attention to this field, too. It is so urgent and necessary to do so to improve the patient compliance to and, thus, the unique curative efficacies of TCM in clinic. In this review, the up-to-date reports in this field were fully summarized with the purpose of providing an informative reference for boosting relevant researches. In general, three types of taste masking techniques were applied to TCM, including, (i) functional masking via sweeteners, bitter blockers, and taste modifiers; (ii) physical masking via polymer film-coating and lipid barrier systems; and (iii) biochemical masking via intermolecular interaction, cyclodextrin inclusion, and ion-exchange resins (Figure 1) [16, 17].