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Biomedical subjects

F Franks

Publications and source records attributed to F Franks.

At least 19 recordsLinked to original sources
PubMed1999

Structural and dynamic properties of crystalline and amorphous phases in raffinose-water mixtures.

PURPOSE: To obtain an improved characterisation of the raffinose-water solid-solid and solid-liquid state diagram, and to study the thermophysical behaviour of the solid amorphous phase. This information is expected to shed light on the potential of raffinose as a pharmaceutical excipient, for stabilising labile preparations at high temperatures. METHODS: X-ray diffraction, scanning electron microscopy, polarised-light microscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were applied to study raffinose pentahydrate and its behaviour during progressive dehydration. RESULTS: Isothermal dehydration of raffinose pentahydrate led to its gradual amorphisation, but also to minor changes in the diffractograms, suggesting the probability of lower stable hydrates. Their existence was confirmed by DSC. Anhydrous raffinose was found to be completely amorphous, and this was supported by the gradual disappearance of birefringence during dehydration. In contrast, electron micrographs, taken during the dehydration process, exhibited no changes in the original ultrastructural crystal morphology. The widths of the glass-to-fluid transitions and the absolute specific heats of crystalline and amorphous phases in the vitreous and fluid states were used to estimate some structural and relaxation characteristics of amorphous raffinose-water mixtures. CONCLUSIONS: Raffinose forms the most "fragile" glass of those pharmaceutical excipients for which data are available. In its thermomechanical properties, it is superior to trehalose and should therefore be effective as a long-term stabiliser for dried biopharmaceutical preparations at temperatures up to 65 degrees C.

Calorimetry, Differential Scanning↗
PubMed1998

Freeze-drying of bioproducts: putting principles into practice.

The product and process parameters that determine successful freeze-drying are described and their interrelationships are explored. It is shown that the thermochemical and thermomechanical properties of water-soluble, amorphous materials form the basis of effective formulation design and that coordinated approaches to formulation and process development achieve optimum results with a minimum of trial-and-error experimentation.

Biological Products↗
PubMed1998

Bond cleavage reactions in solid aqueous carbohydrate solutions.

PURPOSE: To investigate chemical reactivity in water soluble glasses. METHODS: Rates of bond cleavage reactions in freeze-dried and freeze-concentrated aqueous carbohydrate solutions were measured above and below the glass transition temperatures (Tg). The kinetics of two reactions have been determined in formulations containing di- and polysaccharides: (1) fission of the Asp-Pro peptide bond in Physalaemin and Hamburger peptide by following the release of proline, using a ninhydrin based reaction and (2) the unimolecular dissociation of 2-(4-nitrophenoxy) tetrahydropyran by following the release of the 4-nitrophenoxy anion. RESULTS: The results show clearly that reaction occurs below the glass transition temperature, albeit at very reduced rates. No significant enhancement of the temperature dependence of the rate constant was observed near Tg. Different water soluble glasses provide different degrees of stability. The order of stabilisation was sucrose>Ficoll (low mol. weight)>Byco A approximately equal to Ficoll (high mol. weight)>dextran. The density of the matrix, and therefore the degrees of freedom of mobility of the reactant, is thought to be responsible for these differences. CONCLUSIONS: The storage of therapeutic agents, such as proteins, in glassy matrices below Tg does not confer indefinite stability. When formulating products, notice should be taken of the differing stabilisation properties of excipients.

Amino Acid Sequence↗
PubMed1998

The influence of tertiary butyl alcohol and volatile salts on the sublimation of ice from frozen sucrose solutions: implications for freeze-drying.

The purpose of this work was to investigate the phase behavior of tertiary butanol (TBA) and volatile ammonium salts in frozen mixtures with some commonly used excipients and the efficacy of such volatile additives in accelerating the sublimation of ice from frozen solutions. Differential scanning calorimetry was employed to determine first-order phase transformations and glass transition temperatures in binary and ternary mixtures. Ice sublimation rates were studied by conventional freeze-drying and mass loss with time. A eutectic temperature (268 K) was identified for the anhydrous TBA-sucrose system. In frozen ternary water-excipient-TBA systems, the relative amplitudes of the glass and phase transitions, as measured during warming scans, were found to depend critically on the previous cooling rates. Glass transitions of all the freeze-concentrated mixtures used were determined. The sublimation studies indicated an ability of all volatile additives to accelerate ice sublimation from amorphous, freeze-concentrated solutions, but no clear ranking order, applicable to all systems studied, could be established.

Calorimetry, Differential Scanning↗
PubMed1994

Accelerated stability testing of bioproducts: attractions and pitfalls.

Accelerated testing is widely used for the prediction of storage stability and quality, and for the estimation of shelf-lives and 'safe' storage temperatures of labile products. In the food, pharmaceutical and bioindustries, products are stressed by testing at high temperatures. The results are then extrapolated to 'normal' storage conditions. Many such products exist as amorphous solids and are therefore thermodynamically unstable. During accelerated testing, dramatic and sudden physical and/or chemical changes can occur within such products, rendering extrapolation misleading. A knowledge of possible physical changes during heating enables accelerated testing to be performed with confidence.

Biological Products↗
PubMed1992

Cold destabilisation of enzymes.

The thermal stability profile of chymotrypsinogen has been investigated in the temperature range 230-340 K, with special emphasis on the phenomenon of cold instability. Differential scanning calorimetry was used to study the heat capacities of the native and denatured protein in undercooled solution and the results were combined with those obtained by spectrophotometry at ordinary temperatures. The partial heat capacities of both forms decrease with decreasing temperature, assuming negative values. In the experimentally accessible temperature range (above the spontaneous nucleation temperature of ice) the heat capacity difference delta C is found to be positive with a non-linear temperature dependence. delta C is predicted to change sign at some low temperature which cannot, however, be reached by experiment for chymotrypsinogen. In contrast to earlier studies, covering a much more limited temperature range and having to employ an additional destabilisation by means of pH and/or chaotropes, the present findings permit the construction of a more reliable thermodynamic stability profile and related properties. These differ in important details from those reported for other proteins, but based on measurements only in the neighbourhood of the heat-denaturation temperature. The thermodynamic characteristics are, however, in good agreement with earlier predictions and with recent low-temperature measurements on the tetrameric enzyme lactate dehydrogenase.

Calorimetry, Differential Scanning↗
PubMed1992

Freeze-drying: from empiricism to predictability. The significance of glass transitions.

The physical and chemical principles which govern the behaviour of aqueous solutions during freezing and subsequent drying are discussed. They include undercooling, nucleation and growth of ice, the concomitant freeze concentration of the residual solution and its secondary effects, the role of water as plasticizer in amorphous organic materials, the removal of such water, and the over-riding importance of the glass/rubber transition. An understanding of the basic principles can remove most of the empiricism from freeze-drying and lead to more efficient process cycles and to products of superior quality and stability.

Biological Products↗
PubMed1991

Hydration phenomena: an update and implications for the food processing industry.

The past decade has witnessed major revisions in our perception of the manner in which water affects the physical, chemical, and microbiological attributes of all manner of food-related systems. The growing realization that, during processing, most such systems are brought to, and maintained in, a state of thermodynamic instability is focussing attention on the dynamics of the various components in such systems. Older, equilibrium-based concepts, such as "water activity," equilibrium moisture sorption, and "bound" water are being discarded in favour of more appropriate descriptions, in terms of diffusion, nucleation, crystallization and relaxation rates, glass/rubber transitions, and steady states. It is being realized that food processing, materials science, and polymer technology have much in common, with water being the universal plasticizer of naturally occurring organic materials which form the basis of food products.

Carbohydrates↗
PubMed1990

Water, temperature and life.

Cold is the fiercest and most widespread enemy of life on earth. Natural cold adaptation and survival are discussed in terms of physicochemical and biochemical water management mechanisms, relying on thermodynamic or kinetic stabilization. Distinctions are drawn between general effects of low temperature (chill) and specific effects of freezing. Freeze tolerance is a misnomer because tolerance does not extend to the cell fluids. Freezing is confined to the extracellular spaces where it acts as a means of protecting the cytoplasm against freezing injury. Freeze resistance depends on the phenomenon of undercooling, a survival mechanism that relies on the long-term maintenance of a thermodynamically highly unstable state. Correct water management involves many factors, among them the control of membrane composition and transmembrane osmotic equilibrium, the biosynthesis of compounds able to afford protection against injury through freeze desiccation and the availability (or inactivation) of biogenic ice nucleation catalysts.

Adaptation, Physiological↗
PubMed1990

Depression, stress, mastery, and social resources in four ethnocultural women's groups.

This descriptive study was designed to examine the interrelationships of depression, stress, mastery, and social resources in four ethnocultural women's groups. The random sample (N = 212) was comprised of Chinese (n = 60), Vietnamese (n = 46), Portuguese (n = 56), and Latin American (n = 50) immigrant women. Using the CES-D, high depressive symptoms were reported by all groups. Collectively, the major correlates and predictors of depression were perceived stress and mastery. Group-specific analyses revealed different models for predicting depression in each ethnic group. The findings underscore the need for observation of the indicators of depression in immigrant women--regardless of their phase of resettlement--and a flexible, individualized approach to ethnic women's psychological health care.

Adult↗
PubMed1989

The cold-induced denaturation of lactate dehydrogenase at sub-zero temperatures in the absence of perturbants.

The cold-induced denaturation of lactate dehydrogenase has been determined in an unfrozen, cryoprotectant free solution at sub-zero temperatures. The cold-induced denaturation temperature (TL) has been found to be -28 degrees C. The results for the first time clearly establish that temperature alone can induce denaturation in a cooled protein solution. The validity of earlier data, obtained in the presence of perturbants (particularly pH or guanidinium chloride), is discussed.

Animals↗
PubMed1989

The effect of aqueous methanol cryosolvents on the heat- and cold-induced denaturation of lactate dehydrogenase.

The effect on the low-temperature-induced denaturation temperature of various concentrations of methanol has been studied for lactate dehydrogenase. The results have been compared to similar data for the thermal denaturation temperature. Extrapolations of the low-temperature data show that, in a physiological buffer in the absence of methanol, the cold denaturation temperature would be -30 degrees C. Data obtained with high concentrations of methanol indicate that residues are exposed to a similar degree upon either heat- or cold-induced denaturation. Aggregation does not occur in the cold-denatured protein. Cold-induced denaturation is fully reversible at a protein concentration of 250 micrograms/ml. The spectra of the two denatured forms are similar.

Freezing↗
PubMed1989

Salt precipitation during the freeze-concentration of phosphate buffer solutions.

Salt precipitation during the freeze concentration of phosphate solutions was investigated by differential scanning calorimetry (DSC), in view of its practical importance in the cryopreservation or freeze-drying of biological materials. It was found that the fraction of salt precipitated depends on the initial salt concentration; it began to decrease with decreasing concentration at approx. 1 M. Salt precipitation also depends on the cooling rate. In some cases, cooling at approx. 10(3) degree min-1 inhibited salt precipitation which had been observed during slow cooling (0.62 degree min-1), without, however, affecting the shape of the ice melting endotherm. In the case of ternary phosphate buffers, the fraction of salt precipitating depends on the salt composition as well as the initial concentration and cooling rate. Near the composition of the ternary eutectic or the composition where two salts are present at the same concentration, salts were prevented from precipitation.

Buffers↗