title: True density analysis of a freeze-dried amorphous sugar matrix.
abstract: True density of an amorphous matrix represents the state of molecular packing in the matrix, which is closely related to the physical/chemical properties of the material. Dry gas pycnometry is one possible technique for measuring the true density of an amorphous sugar matrix prepared by freeze-drying. We herein report on the influence of conditions used for pycnometry on the measured density value and propose a protocol for obtaining the true density. The technique is sufficiently accurate to permit values for matrices comprised of different types of sugar to be compared. Using the protocol, the true densities of several amorphous sugar samples containing different types of sugar, freeze-drying conditions (temperature and sugar concentration at the time of freezing of an aqueous sugar solution), pretreatment (compaction and grind) were determined and the results were compared. A model for simulating an amorphous matrix of sugar (trehalose) was constructed using molecular dynamics/mechanics calculations, and the true density of the simulated sugar matrix was found to agree with the value experimentally determined using the proposed protocol. The relationship among the true density, the states of intermolecular interactions, and strain of sugar molecules in the matrix are discussed using the simulated amorphous sugar matrix.
authors.affiliation: Department of Bioscience and Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama 700-8530, Japan. kore@cc.okayama-u.ac.jp
authors.forename: Koreyoshi
authors.initials: K
authors.lastname: Imamura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tohru
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Imanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D003198:Computer Simulation; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D005936:Glucans / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D016062:Porosity; D011208:Powders; D012996:Solutions; D013314:Stress, Mechanical; D013678:Technology, Pharmaceutical / Q000379:methods*; D013816:Thermodynamics
chemical_list: D005079:Excipients; D005936:Glucans; D011208:Powders; D012996:Solutions