title: Enhancing the solubility and masking the bitter taste of propiverine using crystalline complex formation.
abstract: BACKGROUND
  Patient compliance can be reduced when bitter-tasting compounds, such as propiverine hydrochloride, are administered orally. Propiverine hydrochloride is an example of a drug with a bitter taste, used for the treatment of overactive bladders.
  
  
  OBJECTIVE
  This study tested whether propiverine free base palatability and aqueous solubility could be improved by crystalline complex formation.
  
  
  METHODS
  We used 42 compounds, and found 9 new propiverine crystalline complexes. The properties and solubility of these complexes were studied using a range of techniques. A taste perception study was carried out using a taste sensor to evaluate the taste masking ability of the crystalline complex formation.
  
  
  RESULTS
  The melting points of the crystalline complexes were higher than that of propiverine. The dissolution rates of the crystalline complexes in aqueous buffer solution (pH 6.8) and in purified water were much faster than that of propiverine. Propiverine salicylic acid crystalline complex had substantially less bitterness than propiverine hydrochloride, which was extremely bitter.
  
  
  CONCLUSIONS
  The present findings indicated that crystalline complex formation provided an effective approach to enhancing propiverine solubility, and to masking its bitter taste.
  
  
  CONCLUSIONS
  Crystalline complex formation represents a useful and valuable technique for the preparation of orally disintegrating tablets and improving patient compliance, even for substances with bitter tastes.
authors.affiliation: Formulation Research Laboratory, Tokushima Research Center, Taiho Pharmaceutical Co., Ltd. , 224-2 Hiraishi-ebisuno, Kawauchi-cho, Tokushima , Japan .
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ogata
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tanaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
mesh_terms: D000284:Administration, Oral; D001561:Benzilates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020156:Salicylic Acid / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013607:Tablets / Q000737:chemistry; D013649:Taste; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D001561:Benzilates; D012996:Solutions; D013607:Tablets; D014867:Water; C015586:propiverine; D020156:Salicylic Acid
keywords: Crystalline complex; dissolution test; propiverine; taste masking; taste sensor