title: The physical state of nafcillin sodium in frozen aqueous solutions and freeze-dried powders.
abstract: The purpose of this study was to develop a better understanding of the physical chemistry of freeze drying of lyotropic liquid crystals using nafcillin sodium as a model solute. Solutions and freeze-dried powders of nafcillin sodium were studied by polarized light microscopy, differential scanning calorimetry, x-ray powder diffraction, and water vapor adsorption. Differential scanning calorimetry thermograms of nafcillin sodium solutions contain a melting endotherm at approximately -5.5 degrees C and, depending on the concentration and heating rate, a crystallization exotherm immediately after this endotherm followed by the melting endotherm of ice. When the sample is annealed at -4 degrees C, both the endotherm and exotherm are eliminated, and a new endotherm appears at approximately -1 degree C on the shoulder of the ice-melting endotherm. The data are interpreted as melting of a liquid crystalline phase, followed by crystallization. X-ray powder diffractograms of unannealed freeze-dried nafcillin sodium are consistent with a lamellar liquid crystal. Diffractograms of annealed freeze-dried nafcillin sodium indicate crystalline material which is a different crystal form than the monohydrate starting material. Moisture adsorption isotherms of the freeze-dried annealed (crystalline) and unannealed (liquid crystalline) nafcillin sodium show different affinities for moisture compared to the crystalline starting material. Solid-state stability data demonstrate that the freeze-dried liquid crystalline form of nafcillin sodium is much less stable than the freeze-dried crystal-line material. The literature recognizes two types of solute behavior on freezing, where the solute either crystallizes from the freeze concentrate or remains amorphous. Lyotropic liquid crystal formation during freezing represents a separate category of freezing behavior, the physical chemistry of which is worthy of further investigation.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
authors.forename: N
authors.initials: N
authors.lastname: Milton
authors.forename: S L
authors.initials: SL
authors.lastname: Nail
mesh_terms: D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D005612:Freeze Drying; D008853:Microscopy; D009254:Nafcillin / Q000737:chemistry*; D010406:Penicillins / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D011208:Powders; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D010406:Penicillins; D019999:Pharmaceutical Solutions; D011208:Powders; D009254:Nafcillin