Biomedical subjects

Harry G Brittain

Publications and source records attributed to Harry G Brittain.

6 recordsLinked to original sources

PubMed2007

Polymorphism and solvatomorphism 2005.

Papers and patents that deal with polymorphism (crystal systems for which a substance can exist in structures characterized by different unit cells, but where each of the forms consists of exactly the same elemental composition) and solvatomorphism (systems where the crystal structures of the substance are defined by different unit cells, but where these unit cells differ in their elemental composition through the inclusion of one or molecules of solvent) have been summarized in an annual review. The works cited in this review were published during 2005, and were drawn primarily from the major physical, crystallographic, and pharmaceutical journals. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and United States patents issued during 2005.

Chemistry, Pharmaceutical↗

PubMed2005

Solid-state fluorescence of the trihydrate phases of ampicillin and amoxicillin.

The purpose of this work was to study the effects of crystal structure on the solid-state photoluminescence of the trihydrate phases of ampicillin and amoxicillin, and to contrast these spectra with analogous spectra obtained on the molecules dissolved in a solution phase. The polymorphic identity of the analytes was established using x-ray powder diffraction and Fourier transform infrared absorption spectroscopy, and the solid-state luminescence spectra obtained under ambient conditions. It was found that the solid-state excitation and emission spectra of ampicillin trihydrate and amoxicillin trihydrate were dominated by energy transfer and exciton effects, which were manifested as decreases in the energy of the excitation and emission bands of the solid-state systems relative to those of the free molecule in solution. The photoluminescence data revealed that in spite of the known structural similarity of ampicillin trihydrate and amoxicillin trihydrate, the magnitude of the Davydov splitting, and the degree of band energy shifting differed between the 2 systems. This finding indicates that the small differences in crystal structure existing between the 2 compounds leads to measurable differences in the patterns of energy transfer.

Amoxicillin↗

PubMed2005

Solid-state fluorescence studies of some polymorphs of diflunisal*.

PURPOSE: The solid-state luminescence spectroscopy of organic molecules is strongly affected by the effects of excited state energy transfer, with the fluorescence of solids often differing significantly from the fluorescence of the molecule dissolved in a solution phase. Because the magnitude of these solid-state effects is determined by the crystallography of the system, solid-state fluorescence studies can be used to gain insight into the polymorphism of the system. To this end, the spectroscopic properties of four polymorphs of diflunisal have been obtained, and compared to the properties of the molecule in the solution phase. METHODS: Fluorescence excitation and emission spectra were obtained on four polymorphic forms of diflunisal, and on the compound dissolved in water. RESULTS: It was found that exciton effects dominate the excitation spectra of diflunisal in the four studied polymorphic forms. These phenomena lead to a decrease in the energy of the excitation bands relative to that observed for the free molecule in fluid solution, and in a splitting of the excitation peak into two Davydov components. CONCLUSIONS: The trends in the excitation and emission spectra led to the grouping of diflunisal Forms I, II, and III into one category, and diflunisal Form IV into a separate category. Because other work has established that Form IV is characterized by the highest crystal density and consequent degree of intermolecular interaction, the magnitude of the exciton coupling can be used to estimate the degree of face-to-face overlap of the salicylate-type fluorophores.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

Foundations of chemical microscopy. 3. Derivatives of some chiral phenylalkylamines and phenylalkylamino acids with 5-nitrobarbituric acid.

At one time, 5-nitrobarbituric acid (also known as dilituric acid) was extensively used as a chemical reagent for the qualitative identification of a variety of basic substances by light microscopy. This methodology was based on evaluation of observed crystal morphologies, because skilled observers could associate a unique crystal habit with the products formed with analytes when those were crystallized using standardized methods. As part of a study to understand the scientific foundations that permitted chemical microscopy to function as a useful analytical technique during its heyday, the products formed by dilituric acid with resolved and racemic phenylalkylamines and phenylalkylamino acids were characterized using a variety of physical analytical techniques. It was found that the different crystal morphologies associated with each of the crystalline adducts were derived from the ability of the systems to form differing structural types and/or hydrate crystal forms upon crystallization.

Alkylation↗

PubMed2004

Fluorescence studies of the transformation of carbamazepine anhydrate form III to its dihydrate phase.

It has been found that both the anhydrous Form III and dihydrate phases of carbamazepine exhibit fluorescence in the solid state. The fluorescence intensity associated with the dihydrate phase was determined to be significantly more intense than that associated with the anhydrate phase, and this difference was exploited to develop a method for study of the kinetics of the aqueous solution-mediated phase transformation between these forms. Studies were conducted at temperatures over the range 18-40 degrees C, and it was found that the phase transformation was adequately characterized by first-order reaction kinetics. The temperature dependence in the calculated rate constants was used to calculate an activation energy of 11.2 kcal/mol (47.4 cal/g) for the anhydrate-to-dihydrate phase conversion.

Algorithms↗

PubMed2002

Effects of mechanical processing on phase composition.

One factor that must be considered during drug development process is that various types of pharmaceutical manufacturing can alter the physical characteristics of the drug entity. These effects become particularly important during scale-up of processing operations, because new and unanticipated results can become manifest in systems of insufficient characterization. Any transformed drug substance or altered dosage form could exhibit an altered solubility or dissolution rate that might produce an undesirable bioavailability profile. Some of the more interesting mechanical manipulations that have the potential to yield problems include particle size reduction and compression, and such investigations are the focus of this minireview.

Compressive Strength↗