title: Synergetic Role of Hypromellose and Methacrylic Acid Copolymer in the Dissolution Improvement of Amorphous Solid Dispersions.
abstract: Synergetic role of polymer blending on dissolution of amorphous solid dispersion was investigated. Dissolution rates of hypromellose (HPMC) and methacrylic acid copolymer (EUD) from the HPMC/EUD spray-dried sample (SPD) were improved compared to those of each single polymer SPD. Differential scanning calorimetry measurements revealed that the structural change in HPMC following heating was inhibited by co-spray-drying with EUD, suggesting an intermolecular interaction between the polymers.13C solid-state nuclear magnetic resonance (NMR) spectroscopy detected the change induced in the hydroxyl group of HPMC by co-spray-drying with EUD. Moreover, the carbonyl peak shape of EUD in the13C NMR spectra differed between EUD SPD and HPMC/EUD SPD, indicating that the dimer structure of the carboxylic acid of EUD was partially disrupted by the interaction with HPMC. An intermolecular interaction occurred between HPMC and EUD. The hydrogen bond reformation likely improved the dissolution rates of the polymers. The ternary griseofulvin (GRF)/HPMC/EUD SPD showed a significantly higher supersaturation level of GRF than the mixtures containing equal amounts of binary GRF/HPMC and GRF/EUD SPDs. The change of interaction mode between polymers improved the dissolution of solid dispersion. Therefore, polymer blending based on interpolymer interactions could be a practical strategy for designing excellent solid dispersion formulations.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ohyagi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kenjirou
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibaraki 305-0044, Japan.
authors.forename: Kohsaku
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan. Electronic address: moribe@faculty.chiba-u.jp.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Moribe
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004357:Drug Synergism; D065347:Hypromellose Derivatives / Q000737:chemistry / Q000378:metabolism*; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility
chemical_list: D008689:Methacrylates; D011108:Polymers; C008384:methacrylic acid; D065347:Hypromellose Derivatives
keywords: calorimetry (DSC); dissolution rate; solid dispersion; solid-state NMR; spray drying