title: Optimization of a novel wax matrix system using aminoalkyl methacrylate copolymer E and ethylcellulose to suppress the bitter taste of acetaminophen.
abstract: The purpose of the present study was to design and evaluate a novel wax matrix system containing various ratios of aminoalkyl methacrylate copolymer E (AMCE) and ethylcellulose (EC) as functional polymers in order to achieve the optimal acetaminophen (APAP) release rate for taste masking. A two factor, three level (3(2)) full factorial study design was used to optimize the ratios of AMCE and EC, and the release of APAP from the wax matrix was evaluated using a stationary disk in accordance with the paddle method. The disk was prepared by congealing glyceryl monostearate (GM), a wax with a low melting point, with various ratios of polymers and APAP. The criteria for release rate of APAP from the disk at pH 4.0 and pH 6.5 were calculated to be more than 0.5017 microg/(mlxmin) and less than 0.1414 microg/(mlxmin), respectively, under the assumption that the particle size of spherical matrix should be 100 microm. In multiple regression analysis, the release of APAP at pH 4.0 was found to increase markedly as the concentration of AMCE increased, whereas the release of APAP at pH 6.5 decreased as the EC concentration increased, even when a high level of AMCE was incorporated. Using principle component analysis, it was found that the viscosity of the matrix affects the pH-dependent release of APAP at pH 4.0 and pH 6.5. Furthermore, using multiple regression analysis, the optimum ratio of APAP:AMCE:EC:GM was found to be 30:7:10:53, and the release pattern of APAP from the optimum wax formulation nearly complied with the desired criteria. Therefore, the present study demonstrated that the incorporation of AMCE and EC into a wax matrix system enabled the appropriate release of APAP as a means of taste masking.
authors.affiliation: Department of Pharmaceutical Engineering, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Kai
authors.initials: K
authors.lastname: Shiino
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Iwao
authors.forename: Atsuo
authors.initials: A
authors.lastname: Miyagishima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Itai
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D010316:Particle Size; D010470:Perceptual Masking; D011109:Polymethacrylic Acids / Q000737:chemistry*; D025341:Principal Component Analysis; D012044:Regression Analysis; D012995:Solubility; D013649:Taste; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity; D014885:Waxes
chemical_list: D018712:Analgesics, Non-Narcotic; D004304:Dosage Forms; D005079:Excipients; D005989:Glycerides; D011109:Polymethacrylic Acids; D014885:Waxes; C048159:glyceryl monostearate; D000082:Acetaminophen; C013517:ethyl cellulose; D002482:Cellulose; C518398:Eudragit E PO