Evaluation of bitterness suppression of macrolide dry syrups by jellies.

The purpose of this study was to evaluate the bitterness-suppressing effect of three jellies, all commercially available on the Japanese market as swallowing aids, on two dry syrups containing the macrolides clarithromycin (CAM) or azithromycin (AZM). The bitterness intensities of mixtures of the dry syrups and acidic jellies were significantly greater than those of water suspensions of the dry syrups in human gustatory sensation tests. On the other hand, the mixture with a chocolate jelly, which has a neutral pH, was less bitter than water suspensions of the dry syrups. The bitterness intensities predicted by the taste sensor output values correlated well with the observed bitterness intensities in human gustatory sensation tests. When the concentrations of CAM and AZM in solutions extracted from physical mixtures of dry syrup and jelly were determined by HPLC, concentrations in the solutions extracted from mixtures with acidic jellies were higher than those from mixtures with a neutral jelly (almost 90 times higher for CAM, and almost 7-10 times higher for AZM). Thus, bitterness suppression is correlated with the pH of the jelly. Finally, a drug dissolution test for dry syrup with and without jelly was performed using the paddle method. There was no significance difference in dissolution profile. It was concluded the appropriate choice of jelly with the right pH is essential for taste masking. Suitable jellies might be used to improve patient compliance, especially in children. The taste sensor may be used to predict the bitterness-suppressing effect of the jelly.

[1]  Y. Katsuragi,et al.  Basic Studies for the Practical Use of Bitterness Inhibitors: Selective Inhibition of Bitterness by Phospholipids , 1997, Pharmaceutical Research.

[2]  Y. Kawashima,et al.  Method of evaluation of the bitterness of clarithromycin dry syrup. , 2002, Chemical & pharmaceutical bulletin.

[3]  Takahiro Uchida,et al.  The bitterness intensity of clarithromycin evaluated by a taste sensor. , 2003, Chemical & pharmaceutical bulletin.

[4]  Hidekazu Ikezaki,et al.  Prediction of the bitterness of single, binary- and multiple-component amino acid solutions using a taste sensor. , 2002, International journal of pharmaceutics.

[5]  Takahiro Uchida,et al.  Bitterness evaluation of medicines for pediatric use by a taste sensor. , 2004, Chemical & pharmaceutical bulletin.

[6]  Tony Nunn,et al.  Formulation of medicines for children. , 2005, British journal of clinical pharmacology.

[7]  Takahiro Uchida,et al.  Quantitative Prediction of the Bitterness Suppression of Elemental Diets by Various Flavors Using a Taste Sensor , 2003, Pharmaceutical Research.

[8]  T. Hanawa,et al.  New oral dosage form for elderly patients. II. Release behavior of benfotiamine from silk fibroin gel. , 1995, Chemical & pharmaceutical bulletin.

[9]  Hidekazu Ikezaki,et al.  Evaluation of the bitterness of antibiotics using a taste sensor , 2003, The Journal of pharmacy and pharmacology.

[10]  國郎 小笠原,et al.  Chem. Pharm. Bull.(オピニオン) , 2007 .

[11]  G. Blumenstock,et al.  Compliance of German pediatric patients with oral antibiotic therapy: results of a nationwide survey. , 1999, The Pediatric infectious disease journal.

[12]  T. Uchida,et al.  Effective Bitterness Evaluation of Macrolide Dry Syrup Formulations by a Taste Sensor , 2005 .

[13]  T. Yajima,et al.  Particle Design for Taste-Masking Using a Spray-Congealing Technique , 1996 .

[14]  S. Itai,et al.  In vitro dissolution tests corresponding to the in vivo dissolution of clarithromycin tablets in the stomach and intestine. , 1995, Chemical & pharmaceutical bulletin.

[15]  N. Iwai Drug compliance of children and infants with oral antibiotics for pediatric use , 1997, Acta paediatrica Japonica : Overseas edition.