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Biomedical subjects

H G Brittain

Publications and source records attributed to H G Brittain.

At least 19 recordsLinked to original sources
PubMed2001

Crystalline solids.

Many drugs exist in the crystalline solid state due to reasons of stability and ease of handling during the various stages of drug development. Crystalline solids can exist in the form of polymorphs, solvates or hydrates. Phase transitions such as polymorph interconversion, desolvation of solvate, formation of hydrate and conversion of crystalline to amorphous form may occur during various pharmaceutical processes, which may alter the dissolution rate and transport characteristics of the drug. Hence it is desirable to choose the most suitable and stable form of the drug in the initial stages of drug development. The current focus of research in the solid-state area is to understand the origins of polymorphism at the molecular level, and to predict and prepare the most stable polymorph of a drug. The recent advances in computational tools allow the prediction of possible polymorphs of the drug from its molecular structure. Sensitive analytical methods are being developed to understand the nature of polymorphism and to characterize the various crystalline forms of a drug in its dosage form. The aim of this review is to emphasize the recent advances made in the area of prediction and characterization of polymorphs and solvates, to address the current challenges faced by pharmaceutical scientists and to anticipate future developments.

Chemistry, Pharmaceutical↗
PubMed1999

Foundations of chemical microscopy, 2 derivatives of primary phenylalkylamines with 5-nitrobarbituric acid.

5-Nitrobarbituric acid (dilituric acid) was extensively used with great success as a chemical microscopic reagent for the qualitative identification of primary phenylalkylamines. This methodology was based on the characterization of observed crystal morphologies, since a unique crystal habit could be associated with each adduct product. To understand the scientific foundations which permitted chemical microscopy to function as a useful analytical technique, the products formed between dilituric acid and a series of primary phenylalkylamines were characterized using polarizing optical microscopy, powder X-ray diffraction, thermal analysis, and solid-state nuclear magnetic resonance. It was deduced that the origins of the different crystal morphologies associated with each of the crystalline adducts arose from the ability of the systems to form differing structural types and/or hydrates upon crystallization. The degree of hydration in the crystalline phenylalkylamine adducts appeared to increase as additional carbon atoms were added between the aromatic ring and the terminal amine group of the aliphatic sidechain.

Barbiturates↗
PubMed1998

Applications of chiroptical spectroscopy for the characterization of pharmaceutical compounds.

Many pharmaceutical compounds contain one or more centers of dissymmetry, thus presenting a unique series of regulatory and compendial requirements. Although most often characterized using chiral chromatography, these molecules can be effectively studied using the various techniques of chiroptical spectroscopy. Techniques which have been found to be very useful for such work include polarimetry, optical rotatory dispersion, circular dichroism, and circularly polarized luminescence. The principles underlying each effect will be briefly outlined, and the application of each illustrated through the inclusion of appropriate examples.

Chemistry, Pharmaceutical↗
PubMed1997

Foundations of chemical microscopy. 1. Solid-state characterization of 5-nitrobarbituric acid (dilituric acid) and its complexes with group IA and group IIA cations.

5-Nitrobarbituric acid (dilituric acid) has been used as a chemical microscopic reagent for the qualitative identification of alkali metal (Group IA) and alkaline earth (Group IIA) cations. This methodology was based on the characterization of observed crystal morphologies, since a unique crystal habit could be associated with each adduct product. To understand the scientific foundations which permitted chemical microscopy to function as a useful analytical technique, the products formed between dilituric acid and the Group IA and IIA cations were characterized using polarizing optical microscopy, powder X-ray diffraction, thermal analysis and solid-state nuclear magnetic resonance. It was found that the origins of the different crystal morphologies associated with each of the adduct arose from the ability of the systems to form various hydrate species, which could also contain structural variations due to cation/diliturate packing patterns.

Barbiturates↗
PubMed1996

Stability of revex, nalmefene hydrochloride injection, in injectable solutions.

The short-term stability of Revex, nalmefene hydrochloride injection, was determined in a number of diluents commonly employed for intravenous use. An HPLC method was used to follow the potency of the diluted solutions, and was fully validated for its intended concentration range prior to its use. Dilutions of Revex were prepared separately in 0.9% sodium chloride injection, 0.45% sodium chloride injection, 5% dextrose injection, 5% dextrose and 0.45% sodium chloride injection, lactated Ringer's injection, 5% dextrose and lactated Ringer's injection and 5% sodium hydrogencarbonate injection. Each admixture was stored at 4 degrees C, room temperature (21 degrees C) and 40 degrees C, with samples being tested after storage at each temperature for 0, 24, 48 and 72 h. Defining stability as the retention of at least 95% of the initial drug concentration at the end of the storage period, it was concluded that the diluted solutions of Revex were uniformly stable for up to 72 h in all of the injectable solutions maintained at either 4, 21 or 40 degrees C.

Chromatography, High Pressure Liquid↗
PubMed1995

The determination of palladium in fosinopril sodium (monopril) by ICP-MS.

A rapid, sensitive ICP-MS method was developed to determine palladium in fosinopril sodium. The assay could not be carried out in a purely aqueous solvent owing to the instability of the palladium species in this media. It was found that the most appropriate vehicle for solubilization of this material was a solution of 25% (v/v) 2-butoxyethanol and water. A minimum quantifiable limit of 0.1 microns g-1 for Pd in the sample (corresponding to 1 ng Pd mL-1 in the analyte solution) was obtained.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effect of humidity-dependent changes in crystal structure on the solid-state fluorescence properties of a new HMG-CoA reductase inhibitor.

It has been shown previously that the disodium salt of a new HMG-CoA reductase inhibitor (SQ-33600) is capable of existing as a number of hydrate species [1]. Three crystalline solid hydrates and one liquid crystalline phase have been identified, each having a definite stability over a defined range of humidity. These forms have been found to exhibit varying fluorescence properties in their respective solid states, with differences in bandshapes and intensities being noted for each. These spectral variations have been correlated with the known pseudopolymorphism of the compound.

Anticholesteremic Agents↗
PubMed1993

Changes in material properties accompanying the national formulary (NF) identity test for microcrystalline cellulose.

It has been found that the current NF identity test for microcrystalline cellulose is actually an assay of the response of the material to energy dissipation expended during the analysis procedure. The blending step needed to effect suspension of the material results in a disintegration of the microcrystalline particles and a concomitant increase in the viscosity of the slurry viscosity. These effects were shown not to be unique functions of either blender speed or blending time. The passage or failure of a given sample of microcrystalline cellulose under the conditions of the identity test was found to be a consequence of the test conditions used. Any given sample of microcrystalline cellulose can be made to pass the identity test if it is blended for a sufficiently long time or at a sufficiently high speed. The test is sufficient, however, to differentiate powdered cellulose from powdered cellulose.

Cellulose↗
PubMed1991

Physical characterization of pharmaceutical solids.

A general review of the methods available for the physical characterization of pharmaceutical solids is presented. The techniques are classified as being on the molecular level (properties capable of being detected in an ensemble of individual molecules), the particulate level (properties which can be detected through the analysis of an ensemble of particles), and the bulk level (properties which can be measured only using a relatively large amount of material). The molecular-level properties discussed are infrared spectroscopy and nuclear magnetic resonance spectrometry, the particulate-level properties discussed are particle morphology, particle size distribution, powder X-ray diffraction, and thermal methods of analysis, and the bulk-level properties discussed are surface area, porosity and pore size distribution, and powder flow characteristics. Full physical characterization of three modifications of lactose (hydrous, anhydrous, and Fast-Flo) is presented to illustrate the type of information which can be obtained using each of the techniques discussed.

Magnetic Resonance Spectroscopy↗
PubMed1990

Crystallographic consequences of molecular dissymmetry.

The molecular chirality associated with an optically active molecule is manifested in the bulk crystallography of the compound. The historical development of optical activity was greatly aided by systematic studies of the habits of enantiomorphic crystals. The concepts of molecular dissymmetry, crystallography, and chirality are therefore linked. Racemic materials can be characterized by means of their melting-point phase diagrams, and this information used to design rational separations of racemic mixtures into their component enantiomers. Certain compounds are found to resolve spontaneously upon crystallization, and the enantiomers of these conglomerate species may be separated by direct crystallization. Compounds which crystallize as true racemates require resolution through the formation and separation of dissociable diastereomer species. The choice of resolution pathway is therefore determinable through an evaluation of the melting-point phase diagrams. When possible, resolution through direct crystallization represents the simplest, most cost-effective means of enantiomer resolution.

Crystallography↗
PubMed1990

Ultraviolet (UV) absorption and circular dichroism (CD) spectra of captopril.

The ultraviolet and circular dichroism spectra of authentic captopril have been obtained, since the reported literature data are inconsistent with those obtained on highly purified material. The UV absorption spectrum consists of a single band maximum at 200 nm, while the CD spectrum consists of a single negative peak located at 210 nm. The CD spectrum of captopril and its other three diastereomers can be explained largely in terms of a summation of the chirality of its individual components, (S)-proline and (2S)-3-mercapto-2-methylpropionic acid.

Captopril↗
PubMed1989

Body fluid analysis of a phosphonic acid angiotensin-converting enzyme inhibitor using high-performance liquid chromatography and post-column derivatization with o-phthalaldehyde.

A method is described for the extraction of a phosphonic acid angiotensin-converting enzyme inhibitor from either urine or plasma, and subsequent quantitation using high-performance liquid chromatographic (HPLC) analysis and post-column o-phthalaldehyde reagent derivatization. The compound cannot be quantitatively extracted from the body fluids, but use of a fluorinated internal standard allowed for the computation of accurate results. With the use of an internal standard, excellent precision, linearity, and recovery were obtained for analyte response in both urine and plasma. In urine a working range of 0.2-10 micrograms/ml was found, with a limit of detection of 0.1 micrograms/ml. For plasma the working range was found to be 2-500 ng/ml, and the limit of detection was established as 1 ng/ml. Due to the non-polar character of the analyte at low pH values, it was possible to use novel extraction (solid-phase C8 column) and HPLC [poly(styrenedivinyl benzene) HPLC column] conditions to separate and quantitate the compound from plasma and urine.

Chemical Phenomena↗
PubMed1977

Circularly polarized emission studies on Tb3+ and Eu3+ complexes with potentially terdentate amino acids in aqueous solution.

Circularly polarized emission (CPE) and total emission (TE) spectra are reported for Eu3+ and Tb3+ complexes of L-aspartic acid (L-asp), L-serine (L-ser), L-threonine (L-thr) and L-histidine (L-his) in D2O solution under various pH conditions. Variations in TE and CPE intensities and in CPE splittings and sign patterns as functions of solution pH are correlated with lanthanide ion/ligand binding characteristics and with structural changes in the coordination environment of the metal ion. In the Eu3+/amino acid systems, the emission bands associated with the 5D0 leads to 7F1 and 7F2 Eu3+ transitions are monitored, and in the Tb3+/amino acid systems the 5D4 leads to 7F5 Tb3+ emission is examined.

Amino Acids↗