Selection of the Best Tasting Matrix: Application to food products for pediatric drug

Objective

When pharmaceutical laboratories have difficulties to formulate pediatric drugs in an easy to administrate forms such as syrups, they can recommend to take the medicines in food matrices in order to mask their bitterness. The objective of this study was to investigate various food vehicles that would be suitable for masking the bad taste of a pediatric drug, and to select the product that achieves the best masking.

Taste Assessment of Pharmaceutical Products with ASTREE E-TONGUE

Working Principle of Electronic Tonguecompared to Human Taste

Microsoft Word - AP09_Food_matrix_for_pediatric_drug.doc

 

Electronic Tongue Analyzer

Microsoft Word - AP09_Food_matrix_for_pediatric_drug.doc

1.  16 or 48 position Autosampler (80 or 15 mL beakers).

2.  Array of 7 electrochemical sensors (cross-selective & partially specific) + 1 reference electrode è potentiometric measurement.

3. Electronic unit for acquisition & autosampler

Experimental Conditions & Samples

After having selected 5 food matrices available on the market (water, fruit compote, 2 different yoghurts, milk), two samples were prepared for each matrix: a placebo consisting of the pure food product and a sample containing the food mixed with a fixed quantity (10 mg/mL) of pharmaceutical active principle (API). The 10 samples obtained were diluted at 1/5 (volume) in demineralized water and then analyzed with the ASTREE Electronic Tongue.

Sample set

Microsoft Word - AP09_Food_matrix_for_pediatric_drug.doc

E-Tongue Analytical  Conditions

Sample volume :                                 25mL

Sample temperature :                          ambient

Time per analysis :                              180s

Acquisition time:                                 120s

 

 Taste Proximity Quantification

Microsoft Word - AP09_Food_matrix_for_pediatric_drug.doc

Fig.2: Distance and discrimination index for each pair (pure matrix –matrix + API)

To evaluate the taste differences between each pure food matrix and the same matrix containing API, an Euclidean distance was calculated for each pair of samples. The shortest the distance, the lower the taste difference and the better the masking effect of the matrix.

A  discrimination index (in %) was also calculated to assess results significance. When discrimination index is below 90%, it can be concluded that there is no statistical difference between the active and the pure matrix.

èWater is the matrix that least masks the API bitterness (highest distance)

èYoghurt 1 & 2 show the lowest distances, but yoghurt 2 has a high discrimination index > 90% (masking not sufficient).

èYoghurt 1 is the product in which the active principle taste is the less perceptible

 

Taste Comparision of The Various Matrices

Microsoft Word - AP09_Food_matrix_for_pediatric_drug.doc

Fig. 1: Principal Component Analysis (PCA) of all samples

The ASTREE measurement showed a high repeatability (Residual Standard Deviation < 2%).

Instrumental results were plotted on a Principal Component Analysis (fig.1) in order to visualize the taste map of all matrices. This map shows the relative distribution and proximity of samples in terms of taste. 

èThe various matrices are clearly differentiated on PC1 axis

èMilk samples are close to the water samples

èYoghurts and compote samples are far from the aqueous samples.

 

Conclusion

Various food products used as a vehicle for drug administration could be rapidly tested using the ASTREE E-Tongue instrument. The study proved that it is possible to safely select a commercial product that will facilitate medicine taking, either for clinical trials or children treatment.

Microsoft Word - AP09_Food_matrix_for_pediatric_drug.doc

 

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