title: Effects of formulation and process factors on the crystal structure of freeze-dried Myo-inositol.
abstract: The objective of this study was to elucidate effects of formulation and process variables on the physical forms of freeze-dried myo-inositol. Physical properties of myo-inositol in frozen solutions, freeze-dried solids, and cooled heat-melt solids were characterized by powder X-ray diffraction (PXRD), thermal analysis (differential scanning calorimetry [DSC] and thermogravimetric), and simultaneous PXRD-DSC analysis. Cooling of heat-melt myo-inositol produced two forms of metastable anhydrate crystals that change to stable form (melting point 225 °C-228 °C) with transition exotherms at around 123 °C and 181 °C, respectively. Freeze-drying of single-solute aqueous myo-inositol solutions after rapid cooling induced crystallization of myo-inositol as metastable anhydrate (transition at 80 °C-125 °C) during secondary drying segment. Contrarily, postfreeze heat treatment (i.e., annealing) induced crystallization of myo-inositol dihydrate. Removal of the crystallization water during the secondary drying produced the stable-form myo-inositol anhydrate crystal. Shelf-ramp slow cooling of myo-inositol solutions resulted in the stable and metastable anhydrous crystal solids depending on the solute concentrations and the solution volumes. Colyophilization with phosphate buffer retained myo-inositol in the amorphous state. Crystallization in different process segments varies crystal form of freeze-dried myo-inositol solids.
authors.affiliation: National Institute of Health Sciences, Setagaya, Tokyo, 158-8501, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Izutsu
authors.forename: Chikako
authors.initials: C
authors.lastname: Yomota
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanishi
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamaki
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ohdate
authors.forename: Zhaokun
authors.initials: Z
authors.lastname: Yu
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yonemochi
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Terada
mesh_terms: D003460:Crystallization; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods*; D007294:Inositol / Q000737:chemistry*; D044367:Phase Transition; D044366:Transition Temperature
chemical_list: D005079:Excipients; D007294:Inositol
keywords: amorphous; crystal polymorphism; crystallization; formulation; freeze-drying; glass transition; physical characterization