title: Oral Sustained Release of a Hydrophilic Drug Using the Lauryl Sulfate Salt/Complex.
abstract: The objective of this study was to establish the key factor of the lauryl sulfate (LS) salt/complex for sustained release of a hydrophilic drug at various physiological pH levels. Mirabegron is a hydrophilic drug that exhibits pH-dependent solubility. Sodium lauryl sulfate (SLS) bound to mirabegron in a stoichiometric manner. The formation of the LS salt/complex significantly reduced mirabegron solubility and helped achieve sustained release of mirabegron over a wide range of pH levels. In addition to SLS, other additives containing a sulfate group formed salts/complexes with mirabegron and reduced its solubility at different pH levels. Furthermore, octyl sulfate (OS), myristyl sulfate (MS), and cetyl sulfate (CS) salts/complexes, which contain alkyl chains of different lengths, showed a lower solubility than mirabegron and promoted sustained release of mirabegron. The rank order of solubility and dissolution rate were as follows: OS salt/complex>LS salt/complex>MS salt/complex>CS salt/complex, which corresponded to the rank of alkyl chain lengths. We conclude that the presence of a sulfate group and the length of the alkyl chain are key factors of the LS salt/complex for sustained release of a hydrophilic drug at various physiological pH levels.
authors: Pharmaceutical and Technology Labs, Astellas Pharma Inc.
authors: Yuuki
authors: Y
authors: Kasashima
authors: Keiichi
authors: K
authors: Yoshihara
authors: Takehiko
authors: T
authors: Yasuji
authors: Kazuhiro
authors: K
authors: Sako
authors: Shinya
authors: S
authors: Uchida
authors: Noriyuki
authors: N
authors: Namiki
mesh_terms: D000083:Acetanilides / Q000008:administration & dosage* / Q000737:chemistry*; D000284:Administration, Oral; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D012492:Salts / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D012995:Solubility; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000083:Acetanilides; D012492:Salts; D013844:Thiazoles; D012967:Sodium Dodecyl Sulfate; C520025:mirabegron