Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that are encountered with certain drugs. Oral administration of bitter drugs with an acceptable degree of palatability is a key issue for health care providers, especially for pediatric patients. Several oral pharmaceuticals, numerous food and beverage products, and bulking agents have unpleasant, bitter-tasting components. So, any pharmaceutical formulation with a pleasing taste would definitely be preferred over a competitor's product and would translate into better compliance and therapeutic value for the patient and more business and profits for the company. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This article reviews the earlier applications and methodologies of taste masking and discusses the most recent developments and approaches of bitterness reduction and inhibition for oral pharmaceuticals.

Taste masking technologies in oral pharmaceuticals: recent developments and approaches.

Herein, we present a survey of the literature covering the development of molecular imprinting science and technology over the years 2004-2011. In total, 3779 references to the original papers, rev ...

Molecular imprinting science and technology: a survey of the literature for the years 2004-2011.

Electronic tongue systems are multisensor devices dedicated to automatic analysis of complicated composition samples and to the recognition of their characteristic properties. Recently, the number of publications covering this topic has significantly increased. Many possible architectures of such devices were proposed: potentiometric, voltammetric, as well as approaches embracing mass- and optical-sensors. For the analysis of sensor array data, various pattern recognition systems were proposed. All of these topics are summarized in this review. Moreover, additional problems are considered: miniaturization of electronic tongues and hybrid systems for liquid sensing.

Sensor arrays for liquid sensing – electronic tongue systems

Effective R&D and strict quality control of a broad range of foods, beverages, and pharmaceutical products require objective taste evaluation. Advanced taste sensors using artificial-lipid membranes have been developed based on concepts of global selectivity and high correlation with human sensory score. These sensors respond similarly to similar basic tastes, which they quantify with high correlations to sensory score. Using these unique properties, these sensors can quantify the basic tastes of saltiness, sourness, bitterness, umami, astringency and richness without multivariate analysis or artificial neural networks. This review describes all aspects of these taste sensors based on artificial lipid, ranging from the response principle and optimal design methods to applications in the food, beverage, and pharmaceutical markets.

Advanced Taste Sensors Based on Artificial Lipids with Global Selectivity to Basic Taste Qualities and High Correlation to Sensory Scores

Phospholipids become increasingly important as formulation excipients and as active ingredients per se. The present article summarizes particular features of commonly used phospholipids and their application spectrum within oral drug formulation and elucidates current strategies to improve bioavailability and disposition of orally administered drugs. Advantages of phospholipids formulations not only comprise enhanced bioavailability of drugs with low aqueous solubility or low membrane penetration potential, but also improvement or alteration of uptake and release of drugs, protection of sensitive active agents from degradation in the gastrointestinal tract, reduction of gastrointestinal side effects of non-steroidal anti-inflammatory drugs and even masking of bitter taste of orally applied drugs. Technological strategies to achieve these effects are highly diverse and offer various possibilities of liquid, semi-liquid and solid lipid-based formulations for drug delivery optimization.

Phospholipids and lipid-based formulations in oral drug delivery.

The purpose of this study was to quantify the degree of suppression of the perceived bitterness of quinine by various substances and to examine the mechanism of bitterness suppression. The following compounds were tested for their ability to suppress bitterness: sucrose, a natural sweetener; aspartame, a noncaloric sweetener; sodium chloride (NaCl) as the electrolyte; phosphatidic acid, a commercial bitterness suppression agent; and tannic acid, a component of green tea. These substances were examined in a gustatory sensation test in human volunteers, a binding study, and using an artificial taste sensor. Sucrose, aspartame, and NaCl were effective in suppressing bitterness, although at comparatively high concentrations. An almost 80% inhibition of bitterness (calculated as concentration %) of a 0.1 mM quinine hydrochloride solution required 800 mM of sucrose, 8 mM of aspartame, and 300 mM NaCl. Similar levels of bitterness inhibition by phosphatidic acid and tannic acid (81.7, 61.0%, respectively) were obtained at much lower concentrations (1.0 (w/v)% for phosphatidic acid and 0.05 (w/v)% for tannic acid). The mechanism of the bitterness-depressing effect of phosphatidic acid and tannic acid was investigated in terms of adsorption and masking at the receptor site. With phosphatidic acid, 36.1% of the bitterness-depressing effect was found to be due to adsorption, while 45.6% was due to suppression at the receptor site. In the case of 0.05 (w/v)% tannic acid, the total bitterness-masking effect was 61.0%. The contribution of the adsorption effect was about 27.5% while the residual masking effect at the receptor site was almost 33%. Further addition of tannic acid (0.15 (w/v)%), however, increased the bitterness score of quinine, which probably represents an effect of the astringency of tannic acid itself. Finally, an artificial taste sensor was used to evaluate or predict the bitterness-depressing effect. The sensor output profile was shown to reflect the depressant effect at the receptor site rather well. Therefore, the taste sensor is potentially useful for predicting the effectiveness of bitterness-depressant substances.

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The effect of various substances on the suppression of the bitterness of quinine-human gustatory sensation, binding, and taste sensor studies.

The purpose of the present study was to quantify the degree of suppression of the bitterness of two amino acids (L-isoleucine (L-Ile), and L-phenylalanine (L-Phe)) which could be achieved by the addition of various test chemicals, and to examine the mechanism of this bitterness suppression. The test chemicals used were two sweeteners (sucrose, aspartame), NaCl, various acidic (L-aspartic acid, L-glutamic acid), or basic (L-histidine, L-lysine and L-arginine) amino acids, tannic acid and phosphatidic acid. The combination of L-arginine (L-Arg) and NaCl together was the most effective in reducing the bitterness of 100 mM L-Ile and L-Phe solutions in human gustatory sensation tests. Even in bitterness of 0.1 mM quinine solution, L-Arg was also successful in reducing the bitterness. This bitterness-suppression effect was specific to L-Arg and not to the other basic amino acids. No comparable taste-masking effect was observed for the acidic amino acids. The artificial taste sensor failed to predict completely the bitterness-suppressing effect of L-Arg. It seems likely that the bitterness-suppressing effect of L-Arg is mediated not only by binding at the receptor site, but also elsewhere in the process of bitterness perception, such as a direct effect on the sodium channel. It is conjectured that the guanidinium group of L-Arg may interact with sodium channels in taste bud membranes.

https://www.jstage.jst.go.jp/article/cpb/52/2/52_2_172/_pdf

The combination effect of L-arginine and NaCl on bitterness suppression of amino acid solutions.

Screening of bitterness‐suppressing agents for quinine: The use of molecularly imprinted polymers

We selected eight generic drugs of sodium loxoprofen, a nonsteroidal anti-inflammatory drug (NSAID), and examined the dissolution ability of these drugs using the paddle method described in JP XIII.When performing the dissolution test performed on the 1st solution (disintengration test solution, pH 1.2) under the condition of 100 rpm and 37°C, the pioneer drug (Tablet A) was found to completely dissolve within 15 min. Some generic drugs showed almost the same dissolution profiles as the pioneer drug, whereas only one generic drug (Tablet F) showed a slower dissolution profile, a 63.8% release within 15 min.Furthermore, for Tablet A and Tablet F, the dissolution test using the 1st solution was performed at 50 rpm and 37°C. As a result, tablet F did not meet the minimum requirement established by the Ministry of Health and Welfare.The above dissolution tests were performed by the authors at the pharmaceutical laboratory of the School of Pharmaceutical Sciences, Mukogawa Women's University. Such collaboration by pharmacists in hospitals with pharmaceutical college in order to evaluate generic drugs should be more strongly encouraged in the future.

https://www.jstage.jst.go.jp/article/jjphcs1975/26/4/26_4_427/_pdf

Collaboration of Hospital Pharmacists with Pharmaceutical College on Evaluation of Generic Drugs : The Case of Dissolution Test of Sodium Loxoprofen Tablets

Tazuko Ogawa

Papers

The effect of various substances on the suppression of the bitterness of quinine-human gustatory sensation, binding, and taste sensor studies.

The combination effect of L-arginine and NaCl on bitterness suppression of amino acid solutions.

Screening of bitterness‐suppressing agents for quinine: The use of molecularly imprinted polymers

Collaboration of Hospital Pharmacists with Pharmaceutical College on Evaluation of Generic Drugs : The Case of Dissolution Test of Sodium Loxoprofen Tablets