title: The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.
abstract: The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.
authors.affiliation: School of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ishizaka
authors.forename: Sachie
authors.initials: S
authors.lastname: Okada
authors.forename: Eri
authors.initials: E
authors.lastname: Takemoto
authors.forename: Emi
authors.initials: E
authors.lastname: Tokuyama
authors.forename: Eriko
authors.initials: E
authors.lastname: Tsuji
authors.forename: Junji
authors.initials: J
authors.lastname: Mukai
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uchida
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002233:Carbocysteine / Q000737:chemistry / Q000494:pharmacology; D017291:Clarithromycin / Q000737:chemistry / Q000494:pharmacology*; D005421:Flavoring Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology*; D019999:Pharmaceutical Solutions / Q000032:analysis; D011208:Powders; D012995:Solubility; D012996:Solutions; D013535:Suspensions; D013652:Taste Threshold / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D005421:Flavoring Agents; D018942:Macrolides; D019999:Pharmaceutical Solutions; D011208:Powders; D012996:Solutions; D013535:Suspensions; D002233:Carbocysteine; D017291:Clarithromycin