Dehydration Study of Piracetam Co-Crystal Hydrates.

A hydrate of co-crystal of piracetam and 3,5-dihydroxybenzoic acid was obtained via crystallization from water. Single-crystal X-ray data show that piracetam/3,5-dihydroxybenzoic acid tetrahydrate (P35TH) crystallizes in the triclinic system with a P1 space group. The physicochemical properties of co-crystal hydrate were characterized using powder X-ray diffractometry, differential scanning calorimetry (DSC), thermogravimetric analyzer (TGA), and FTIR spectroscopy.

Effect of position isomerism on the formation and physicochemical properties of pharmaceutical co-crystals.

The effect of position isomerism on the co-crystals formation and physicochemical properties was evaluated. Piracetam was used as the model compound. Six position isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acid (DHBA), were used as the co-crystal formers.

Evaluation of the compaction of sulfathiazole polymorphs.

The aim of this study was to relate the tableting performance assessed by an instrumented tableting machine to the mechanical properties measured by nanoindentation. Three different polymorphic forms of sulfathiazole were prepared by recrystallization, and the density and X-ray powder diffraction patterns were measured and compared with theoretical density and simulated powder patterns, respectively. Tablets were prepared using a series of applied pressures, and the results were subjected to energy analysis, three dimensional (3D) modeling, and the traditional Heckel analysis.

Influence of processing conditions on the physical state of mannitol--implications in freeze-drying.

Purpose: To study the effect of processing conditions on the physical state of mannitol during various stages of the lyophilization cycle of a protein formulation.

Materials And Methods: Mannitol and trehalose were used as the bulking agent and lyoprotectant, respectively. The physical state of mannitol during various stages of freeze-drying cycle, in the absence and presence of a model protein, was characterized using low temperature X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC).

Formation of cholesterol crystals at a mucin coated substrate.

Purpose: High-resolution, tapping-mode atomic force microscopy (AFM) was used to monitor the early stage of the formation of cholesterol crystals under simulated conditions of the gallbladder environment.

Methods: AFM images of phosphatidylcholine/cholesterol vesicles were obtained using a mucin-coated mica substrate.

Results: The vesicles appeared flattened with diameters from 100 to 300 nm and heights that varied from 10 to 100 nm.

Synthesis of 2'-C-difluoromethylribonucleosides and their enzymatic incorporation into oligonucleotides.

[Chemical reaction: See text] Nucleosides bearing a branched ribose have significant promise as therapeutic agents and biotechnological and biochemical tools. Here we describe synthetic entry into a new subclass of these analogues, 2'-C-beta-difluoromethylribonucleosides. We constructed the glycosylating agent 4 in three steps from 1,3,5-tri-O-benzoyl-alpha-D-ribofuranose 1.

Influence of the active pharmaceutical ingredient concentration on the physical state of mannitol--implications in freeze-drying.

Purpose: The aim of this study was to investigate the effect of the concentration of the active pharmaceutical ingredient on the physical state of mannitol in frozen aqueous systems.

Methods: A human monoclonal antibody was used as the model protein. Mannitol and sucrose were used as the bulking agent and the lyoprotectant, respectively.

Measurement of process-dependent material properties of pharmaceutical solids by nanoindentation.

The purpose of this work was to evaluate nanoindentation as a means to characterize the material properties of pharmaceutical solids. X-ray diffraction of potassium chloride and acetaminophen showed that samples prepared by cooling a melt to a crystalline sample as opposed to slow recrystallization had the same crystal structure. With analysis of the force-displacement curves, the KCl quenched samples had a hardness that was 10 times higher than the recrystallized KCl, while acetaminophen quenched samples were 25% harder than the recrystallized samples.

Lung distribution of the chemopreventive agent difluoromethylornithine (DFMO) following oral and inhalation delivery.

The inhalation delivery of difluoromethylornithine (DFMO) was evaluated to determine its feasibility for use in lung cancer chemoprevention. Aerosol droplets of DFMO were produced, and the solvent was removed by a reflux drying column. Equivalent doses of DFMO (40 mg/kg) were given over 10 minutes by inhalation and by gavage, and the serum and tissue levels were determined.

Characterization of pharmaceutical solids by scanning probe microscopy.

The force-displacement profiles of four well-characterized materials that represent both soft/hard and plastic/brittle materials have been obtained using a novel nanoindentation technique. Flat surfaces of acetaminophen, potassium chloride, sucrose, and sodium stearate were prepared by melting or recrystallization, and the melting points were measured. Topographic and the corresponding first derivative images were obtained both before and after indentation.

Solubilization of cationic drugs in lung surfactant.

Purpose: The association of hydrophobic, cationic drugs with lung surfactant was determined to assess the pharmacokinetic implications on drug disposition and retention in the lung.

Methods: The distribution coefficients, K, were determined at 25 and 37 degrees in normal saline solution buffered at pH 7.4 for a series of structurally related, cationic drugs.

2'-C-Branched Ribonucleosides: Synthesis of the Phosphoramidite Derivatives of 2'-C-beta-Methylcytidine and Their Incorporation into Oligonucleotides.

We describe a strategy for the incorporation of a 2'-C-branched ribonucleoside, 2'-C-beta-methylcytidine, into oligonucleotides via solid-phase synthesis using phosphoramidite derivatives. 4-N-Benzoyl-2'-C-beta-methylcytidine (2b) was synthesized by coupling persilylated 4-N-benzoylcytosine with 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-alpha-(and beta)-D-ribofuranose (1) in the presence of SnCl(4) in acetonitrile, followed by selective deprotection with NaOH in pyridine/methanol. The 3'- and 5'-hydroxyl groups were blocked as a cyclic di-tert-butylsilanediyl ether 3 by treatment with di-tert-butyldichlorosilane/AgNO(3) in DMF.