Ulrich J. Griesser

NMR crystallography of oxybuprocaine hydrochloride, Modification II°

The (13)C CPMAS spectrum is presented for the polymorph of oxybuprocaine hydrochloride which is stable at room temperature, i.e. Mod. II degrees . It shows crystallographic splittings arising from the fact that there are two molecules, with substantially different conformations, in the asymmetric unit. An INADEQUATE two-dimensional experiment was used to link signals for the same independent molecule. The chemical shifts are discussed in relation to the crystal structure. Of the four ethyl groups attached to NH(+) nitrogens, one gives rise to unusually low chemical shifts, very different from those of the other three ethyl groups. This is attributed empirically to gamma-gauche conformational effects, as is confirmed by shielding computations. These considerations allow (13)C signals to be assigned to specific carbons in the two crystallographically inequivalent molecules in the crystal structure. Indeed, information about the conformations is inherent in the NMR spectrum, which thus provides data of crystallographic significance. A (13)C/(1)H HETCOR experiment enabled resolution to be obtained in the (1)H dimension and allowed (1)H and (13)C signals for the same independent molecule to be linked.

The effect of water vapor pressure on desolvation kinetics of caffeine 4/5-hydrate

Abstract The kinetics of dehydration of caffeine 4/5-hydrate at different relative humidities (RH) was studied at 25°C for two crystal preparations with different crystal sizes. The weight change was evaluated over phosphorus pentoxide and relative humidities of 9, 13, 24, 36 and 43%, using special hygrostats and a below-weight balance. Additionally the samples were stored for 8 months at RH between 0 and 98%. A mechanistic interpretation of the reaction was derived by analyzing the data with numerous kinetic models as well as by microscopic investigations and various thermoanalytical techniques (thermomicroscopy, thermogravimetry, differential scanning calorimetry). The mechanism of the dehydration reaction was found to be very complex, depending on the crystal size and water vapor pressure. Diffusion control as well as nucleation and growth reaction are considered as the fundamental principles of the process. Due to the occurrence of a Smith-Topley effect, a constant loss of water rate of a coarse crystalline batch between 0 and 13% relative humidity takes place. The dehydration rate of small crystals is much more affected by changes in water vapor pressure. Over desiccants, complete transformation to the anhydrate requires about 4 h, a 30th of the time required for the coarse crystals. Caffeine hydrate loses the water of crystallization even at 61% RH (25°C), which should be considered during processing and storing conditions. Beyond that, this paper suggests that a variety of analytical techniques are necessary for sufficient information about the dehydration characteristics of a crystalline hydrate and to avoid misinterpretations of phase transformations in the solid state.

Conformational polymorphism in aripiprazole: Preparation, stability and structure of five modifications

Five phase-pure modifications of the antipsychotic drug aripiprazole were prepared and characterized by thermal analysis, vibrational spectroscopy and X-ray diffractometry. All modifications can be produced from solvents, form I additionally by heating of form X degrees to approximately 120 degrees C (solid-solid transformation) and form III by crystallization from the melt. Thermodynamic relationships between the polymorphs were evaluated on the basis of thermochemical data and visualized in a semi-schematic energy/temperature diagram. At least six of the ten polymorphic pairs are enantiotropically and two monotropically related. Form X degrees is the thermodynamically stable modification at 20 degrees C, form II is stable in a window from about 62-77 degrees C, and form I above 80 degrees C (high-temperature form). Forms III and IV are triclinic (

Advances in pharmaceutical materials and processing

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How good are the crystallisation methods for co-crystals? A comparative study of piroxicam

), I and X degrees are monoclinic (P2(1)) and form II orthorhombic (Pna2(1)). Each polymorph exhibits a distinct molecular conformation, and there are two fundamental N-H

Characterization of cellulosic fibers and fabrics by sorption/desorption

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Spray Drying of Mannitol as a Drug Carrier—The Impact of Process Parameters on Product Properties

O hydrogen bond synthons (catemers and dimers). Hirshfeld surface analysis was employed to display differences in intermolecular short contacts. A high kinetic stability was observed for three metastable polymorphs which can be categorized as suitable candidates for the development of solid dosage forms.

The complexity of hydration of phloroglucinol: a comprehensive structural and thermodynamic characterization.

Abstract Advances in pharmaceutical materials and processing require new generations of pharmaceutical technologies, which in turn require an improved understanding of each step in the unit processes of dosage form development. The unit processes range from raw material qualification to final product release using process monitoring of critical steps. The authors illustrate some recent research trends in understanding and improving pharmaceutical materials and processing through the use of experience obtained within several research programs at Purdue University (West Lafayette, IN, USA).

Solid-state forms of β-resorcylic acid how exhaustive should a polymorph screen be?

Co-crystallisation of two components into one crystal form can enhance the solid-state properties of drug compounds. A plethora of crystallisation methods has been applied to co-crystallisation and the reported study compares the three most common ones (crystallisation from the melt, from solution and solvent-drop grinding) with respect to their applicability and necessity for a co-crystal screening. Piroxicam, a non-steroidal anti-inflammatory drug, was chosen as a model system and submitted to an extensive co-crystal screening using twenty different acids as co-crystal formers, six crystallisation techniques and five solvents. A total of 46 co-crystal forms were obtained, 38 of which are novel. Solvent-drop grinding showed the highest absolute number of experiments resulting in co-crystals, while crystallisation from the melt yielded the highest number of co-crystal formation when crystalline material was obtained. Evaporation resulted in a high number of crystalline products but many of those were binary and ternary mixtures of crystal forms. Cooling and precipitation techniques gave only poor results. Acetone and THF showed the highest number of crystalline products while chloroform gave the highest relative yield of co-crystals. Ethanol and acetonitrile showed extensive hydrate formation. No influence of the co-crystal former on the co-crystal formation could be detected.

Ligand-Based Pharmacophore Modeling and Virtual Screening for the Discovery of Novel 17β-Hydroxysteroid Dehydrogenase 2 Inhibitors

Three cellulosic substrates: lyocell (CLY), viscose (CV), and modal (CMD) in the form of fibers and fabrics were subjected to wet/dry or wash/dry treatments. The accessibility of untreated and treated substrates to water and iodine was investigated using dynamic water-vapor sorption, moisture retention, and iodine sorption methods, to study the influence of treatments on sorption-desorption hysteresis, fraction of moisture sorbed as a monomolecular layer, water retention, and iodine sorption. It was found that the sorption properties of untreated and treated substrates differed with sorbate type as well as substrate type and form.