This thesis investigated the physical properties of the macrolide antibiotics: Erythromycin dihydrate (EM-DH), Roxithromycin monohydrate (RM-MH) and Azithromycin dihydrate (AZM-DH). The abovementioned hydrate compounds were investigated in terms of the hydrate-anhydrate crystal structure stability, dehydration and observed polymorphism under controlled temperature heating programs. Identified hydrate and anhydrate polymorphs were subjected to physical stability testing during controlled storage. EM-DH was characterized by thermal analysis (DSC, TGA), X-ray diffraction, FTIR and microscopy. Dehydration of EM-DH at temperatures of 100, 157 and 200°C (followed by supercooling to 25°C) produced the form (I) anhydrate (Tm =142.9°C), form (II) anhydrate (Tm = 184.7°C ) and amorph (II) (Tg = 118°C) respectively. The attempts to produce amorph (I) from melting (in vicinity of form (I) melt over temperature range 133°C to 144°C) and supercooling was unsuccessful due to the high crystallization tendency of the form (I) melt. Brief humidity exposure and controlled temperature (40°C)/ humidity storage for 4 days (0-96% RH) revealed hygroscopic behaviour for the anhydrate crystal (forms (I) and (II)) and amorph (II) forms. Form (II) converted to a nonstoichiometric hydrate where extent of water vapour absorption increased with increased storage humidity (2.1% absorbed moisture from recorded TGA at 96% RH). Amorph (II) exhibited similar trends but with greater water absorption of 4.7% (recorded with TGA) at 96% RH. The pulverization and sieving process of amorph (II) (at normal environmental conditions) was accompanied by some water vapour absorption (1.1%). A slightly lower absorbed moisture content of 3.3% (from TGA) after controlled 4 days storage at 40°C/ 96% RH was recorded. This suggested some physical instability (crystallization tendency) of amorph (II) after pulverization. The thermally induced dehydration of RM-MH by DSC-TG was evaluated structurally (SCXRD), morphologically (microscopy) and by kinetic analysis. Various kinetic analysis approaches were employed (advanced, approximation based integral and differential kinetic analysis methods) in order to obtain reliable dehydration kinetic parameters. The crystal structure was little affected by dehydration as most H-bonds were intramolecular and not integral to the crystal structure stability. Kinetic parameters from thermally stimulated dehydration indicated a multidimensional diffusion based mechanism, due to the escape of water from interlinked voids in crystal. The hygroscopicity of the forms RM-MH, Roxithromycin-anhydrate and amorph glass (Tg = 81.4°C) were investigated. Roxithromycinanhydrate (crystalline) converted readily to RM-MH which were found to be compositionally stable over the humidity range 43-96%RH. Amorphous glass exhibited increased water vapour absorption with increasing storage humidity (40°C/ 0-96% RH). TG analysis suggested a moisture content of 3.5% at 96% RH after 4 storage days. DSC and powder XRD analysis of stored pulverised amorphous glass indicated some physical instability due to water induced crystallization. Commercial AZM-DH and its modifications were characterized by thermal analysis (DSC, TGA), SC-XRD and microscopy. Thermally stimulated dehydration of AZM-DH occurred in a two-step process over different temperature ranges. This was attributed to different bonding environments for coordinated waters which were also verified from the crystal structure. Dehydration activation energies for thermally stimulated dehydration were however similar for both loss steps. This was attributed to similarities in the mode of H- bonding. Different forms of AZM were prepared by programmed temperature heating and cooling of AZM-DH. The prepared forms included amorphous glass (melt supercooling), amorphous powder (prepared below crystalline melting temperature), crystalline anhydrate and crystalline partial dehydrate. Humidity exposure indicated hygroscopic behaviour for the amorphous, crystalline anhydrate and crystalline partial dehydrate modifications. Both the crystalline anhydrate and partial dehydrate modifications converted to the stoichiometric dihydrate form (AZM-DH) at normal environmental conditions at ambient temperature. Both the amorph glass and amorph powder exhibited increased moisture absorption with increased humidity exposure. TG analysis of the pulverised amorph glass indicated a moisture content of 5.1% at 96% RH after 4 storage days. The absence of crystalline melt in DSC and presence of Tg (106.9°C) indicated the sample remained amorphous after pulverisation and storage for 4 days at 40°C/ 96% RH.

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by Wong Sai-peng. / Bibliography: leaves 116-119 / Thesis (Ph.D)--Chinese University of Hong Kong, 1984

Thesis (M.Phil.)--Chinese University of Hong Kong. / Bibliography: leaves 85-86.

by Choy Juliet. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 142-144). / Text in English; abstract also in Chinese. / by Choy Juliet. / List Of Figures --- p.iii / List of Tables --- p.xxii / Abstract --- p.xxiii / Acknowledgments --- p.xxvi / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Review On Free Bose Gases --- p.6 / Chapter 2.1 --- 3D Free Bose Gas --- p.6 / Chapter 2.2 --- Bose-Einstein Condensation in Three Dimensions --- p.9 / Chapter 2.3 --- Ideal Bose Gas in Two Dimensions [15] --- p.12 / Chapter 3 --- Bose-Einstein Condensation in a 3D cubic box --- p.15 / Chapter 3.1 --- Effects of boundaries on Bose-Einstein Condensation --- p.15 / Chapter 3.2 --- Bose-Einstein condensation in a 3D cubic box --- p.17 / Chapter 3.3 --- Numerical results for bosons in a 3D cubic box --- p.20 / Chapter 4 --- Bosons in harmonic potentials --- p.25 / Chapter 4.1 --- 3D Isotropic harmonic potential --- p.26 / Chapter 4.2 --- 3D Anisotropic harmonic potentials --- p.32 / Chapter 4.3 --- 2D Harmonic potential --- p.37 / Chapter 4.4 --- ID Harmonic potential --- p.42 / Chapter 5 --- Bosons trapped in highly anisotropic harmonic potentials --- p.47 / Chapter 5.1 --- Two-step Condensation in highly anisotropic harmonic traps --- p.48 / Chapter 5.2 --- The freezing out of the degrees of freedom --- p.51 / Chapter 6 --- Bosons in q-deformed potentials --- p.56 / Chapter 6.1 --- The q-deformed harmonic oscillator --- p.57 / Chapter 6.2 --- Condensation of a Bose gas with the q-deformed harmonic oscillator energy spectrum --- p.60 / Chapter 7 --- Rotational and density related properties of trapped bosons: the formalism --- p.77 / Chapter 7.1 --- Rotational properties of trapped bosons --- p.77 / Chapter 7.2 --- Density related properties of trapped bosons --- p.82 / Chapter 8 --- Rotational and density related properties of trapped bosons: results for harmonic and q-deformed oscillators --- p.88 / Chapter 8.1 --- Rotational property of bosons in harmonic andq-deformed potentials --- p.88 / Chapter 8.2 --- Density related properties of bosons in harmonic and q-deformed potentials --- p.103 / Chapter 9 --- Thermal properties of bosons in the field of a superposition of double-well potentials --- p.121 / Chapter 9.1 --- Numerical study of bosons in the field of a superposition of double- well potentials --- p.121 / Chapter 9.2 --- Low temperature thermodynamics of bosons in a double well po- tential --- p.129 / Chapter 10 --- Conclusion --- p.139