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Biomedical subjects

G Zografi

Publications and source records attributed to G Zografi.

At least 55 records · Page 3Linked to original sources
PubMed1993

The use of solution theories for predicting water vapor absorption by amorphous pharmaceutical solids: a test of the Flory-Huggins and Vrentas models.

The limitations of traditional gas adsorption models for describing water vapor sorption by amorphous pharmaceutical solids are described and an alternative approach based on polymer solution theories is proposed. The approach is tested by comparing a priori predicted isotherms with literature data for the poly(vinylpyrrolidone)(PVP)-water system. The well-known Flory-Huggins model is able to describe the water vapor sorption isotherm only when the PVP-water mixture is in the rubbery state (i.e., above its glass transition temperature). However, a newer model developed by Vrentas and coworkers, which takes into account the plasticizing effect of water on the polymer, is able to describe the entire form of the isotherm. Consideration of the parameters in this model allows a number of critical variables to be identified and also enables the characteristic shape of the water vapor sorption isotherm to be explained.

Adsorption↗
PubMed1993

Molecular mobility in mixtures of absorbed water and solid poly(vinylpyrrolidone).

Poly(vinylpyrrolidone) (PVP) was used as model system to examine molecular mobility in mixtures of absorbed water with solid amorphous polymers. Water vapor absorption isotherms were determined, along with diffusion and proton NMR relaxation measurements of absorbed water. Concurrently, measurements of glass transition temperatures (Tg) and carbon-13 NMR relaxation times for PVP were determined as a function of water content. Two water contents were used as reference points: Wm, obtained from the fit of water absorption isotherms to the BET equation, corresponding to the first shoulder in the sigmoid isotherm; and Wg, the amount of water necessary to depress Tg to the isotherm temperature. Translational diffusion coefficients of water, along with proton T1 relaxation time constants, show that both the translational and the rotational mobility of the water is hindered by the presence of the solid polymer and that the absorbed water is most likely represented by two or more populations of water with different modes or time scales of motion. The presence of "tightly bound" or immobilized water at levels corresponding to Wm, however, is unlikely, since water molecules maintain a high degree of mobility, even at the lowest levels of water. Above Wg, water shows an increase in mobility with increasing water content, but it is always less mobile than bulk water. With increasing water content, carbon-13 T1 relaxation time constants for PVP, measured under the same conditions as above, indicate a major increase in the molecular mobility of carbon atoms associated with the pyrrolidone side chains.

Carbon Isotopes↗
PubMed1991

Lung calcium-dependent phospholipid-binding proteins: structure and function.

Distinct peptide maps of two rabbit lung Ca2(+)-dependent phospholipid-binding proteins (PLBPs), 36,000 and 33,000, were generated by cyanogen bromide (CNBr) cleavage, trypsin or Staphylococcus aureus V8 proteinase digestion. The amino acid sequence of a CNBr-cleaved peptide of the 36,000 PLBP was aligned to the amino terminus of human lipocortin I with more than 77% identity, but had no identity with the known amino terminal sequence of other known annexins. Partial amino acid sequence of a 33,000 PLBP peptide demonstrated a close (56%) relationship to endonexin II, human placental anticoagulant protein, and porcine intestine protein II, but shared only 32% identity with lipocortin I, 30% with lipocortin II. Antiserum generated against purified 36,000 PLBP reacted strongly with the 33,000 PLBP, but did not react with any other rabbit lung cytosolic proteins. Both PLBPs inhibited the phospholipase A2 reaction when dioleoyl phosphatidylcholine and phosphatidylglycerol vesicles or monolayers were used as substrates. In the vesicle assay, the phospholipase A2 reaction was inhibited at lower substrate phospholipid concentrations but not at nearly saturating substrate concentrations. In the monolayer assay, the phospholipid-binding proteins did not inhibit phospholipase A2 at a low phospholipid surface concentration of 3.8.10(-3) molecules/A2, but they did at higher surface concentrations between 1.1 x 10(-2) and 3.8 x 10(-2) molecules/A2. The inhibition of phospholipase A2 by rabbit lung phospholipid-binding proteins is most likely due to the prevention of penetration by phospholipase A2 into the interface, a requirement for the enzyme to act on the substrate.

Amino Acid Sequence↗
PubMed1991

Solid-state phase transitions initiated by water vapor sorption of crystalline L-660,711, a leukotriene D4 receptor antagonist.

Significant water vapor sorption at room temperature by the crystalline and lyophilized forms of L-660,711, a potent, selective leukotriene D4 receptor antagonist, has been measured and shown to produce increasingly more nonflowing, semisolid masses with increasing relative humidity. Thermal analysis, SEM, powder X-ray diffraction, solid-state NMR, and thermomicroscopic measurements reveal that water vapor sorbed at room temperature converts the crystalline form to a noncrystalline form resembling the lyophilized sample. Evidence is presented to indicate that L-660,711 has surface active properties with a critical micellization concentration of approximately 1 x 10(-4) M and an ability to form thermotropic and lyotropic mesomorphic phases when the crystal is heated above 80 degrees C in the anhydrous state; it is lyophilized from aqueous solution, and it is exposed to relative humidities at and above 12%, at room temperature.

Calorimetry, Differential Scanning↗
PubMed1990

Uptake of L-carnitine by rat jejunal brush border microvillous membrane vesicles. Evidence of passive diffusion.

We have previously described apparent active transport of carnitine into rat intestinal mucosa with intracellular accumulation against a concentration gradient in a process dependent upon the presence of sodium ions, oxygen, and energy. In the work described here, we sought to define the interaction between carnitine and the brush border membrane, which we presumed contained the transport mechanism. Using isolated rat jejunal brush border microvillous membrane vesicles, we found evidence of passive diffusion alone. We found no evidence of carrier-mediated transport--in particular no saturation over a concentration range, inhibition by structural analogs, transstimulation phenomenon, and no influence of sodium ions, potential difference or proton gradients. We conclude that a carnitine transporter does not exist in the brush border membrane of enterocytes and that other cellular mechanisms are responsible for the apparent active transport observed.

Animals↗
PubMed1990

The use of a multichannel scaling method to detect radioactive species in spread monolayers.

This study describes a simple and inexpensive method for monitoring radioactive species spread as monolayers at the air/water interface. The combination of a discriminator and multichannel scalar counter with a personal computer functions to unify all measurements, to simplify the operational process and data acquisition, and to provide a real-time display of the data. Its use is demonstrated by following the hydrolysis of L-alpha-[1-14C]dioleoyl phosphatidylcholine by the enzyme, phospholipase A2, isolated from the porcine pancreas.

Animals↗
PubMed1990

The relationship between the glass transition temperature and water vapor absorption by poly(vinylpyrrolidone)

Water associated with amorphous solids is known to affect significantly the physical and chemical properties of dosage form ingredients. An analysis of water vapor absorption isotherms of poly(vinylpyrrolidone) measured in this and other laboratories, over the range -40 to 60 degrees C, along with the measurement of the glass transition temperature of poly(vinylpyrrolidone) as a function of water content is reported. It is observed that the amount of water vapor absorbed at a particular relative humidity increases with decreasing temperature, along with a significant change in the shape of the isotherm. It is also shown that at any temperature, along with a significant change in the shape of the isotherm. It is also shown that at any temperature the state of the solid changes from a highly viscous glass to a much less viscous rubber in the region where absorbed water appears to enter into a "solvent-like" state. Further, the apparent "tightly bound" state, observed at low relative humidities, appears to exist when the polymer enters into a very viscous glassy state. It is concluded that the apparent states of water and polymer are interrelated in a dynamic manner and, therefore, that they cannot be uncoupled by simple thermodynamic analyses based only on a water-binding model.

Absorption↗
PubMed1988

Equilibrium uptake of D-glucose by osmotically stressed unilamellar phospholipid vesicles.

The assumptions inherent in the use of osmotic manipulation to determine the extent of solute binding to brush border membrane vesicles (the ideal osmotic responsiveness of the vesicles and the independence of solute binding from the incubation medium osmotic pressure) were examined in a model system (large unilamellar lipid vesicles). The equilibrium uptake of D-glucose by unilamellar vesicles composed of egg lecithin (PC), phosphatidic acid (PA), and cholesterol (Chol) was measured as a function of the osmotic concentration of the incubation medium. The variation of the encapsulated aqueous volume of PC:PA and PC:PA:Chol vesicles with the osmotic stress was directly determined by a fluorescence self-quenching technique. Encapsulated volume changes of both PC:PA and PC:PA:Chol vesicles were found to be resistant to the osmotic stress, exhibiting positive deviations from ideal behavior. Equilibrium uptake experiments with these vesicles showed that glucose was taken up in excess of that amount predicted on the basis of the encapsulated volume when the vesicles were subjected to osmotic stress less than 0.25 osmol/kg. At osmotic stresses greater than 0.75 osmol/kg, equilibrium uptake could be predicted solely on the basis of the encapsulated volume. These results, based on a model vesicle system, strongly suggest that osmotic manipulation may be an inappropriate method to assess the extent of solute binding to natural membrane vesicle preparations, such as brush border membrane vesicles, without more direct evidence.

Cholesterol↗
PubMed1988

The association of D-glucose with unilamellar phospholipid vesicles.

The equilibrium uptake of hydrophilic solutes, D-glucose and L-carnitine, by large unilamellar phospholipid vesicles composed of egg lecithin (PC), phosphatidic acid (PA), and various concentrations of cholesterol (Chol) has been measured. Calculation of the encapsulated volume of PC-PA and PC-PA-Chol vesicles, based on electron-microscopy data, agreed with the values directly measured by fluorescence techniques. Likewise, vesicle surface areas determined directly and from electron microscopy were in good agreement. Equilibrium uptake experiments by these well-characterized vesicles showed that glucose was taken up in excess of that amount predicted on the basis of the encapsulated aqueous volume. In contrast, the equilibrium uptake of carnitine can be predicted solely on the basis of the vesicle encapsulated volume. Each excess glucose molecule was found to be associated with from 7 to 5200 phospholipid molecules for 100 and 0.1 mM glucose, respectively. Uptake of glucose by PC-PA-Chol vesicles is independent of the cholesterol concentration and is similar to that observed in PC-PA vesicles. The cholesterol concentration independence and oil/buffer partitioning studies with octane and octanol, coupled with previous studies, strongly suggest that excess glucose is located in the vicinity of the phospholipid head group. A probable mechanism would have phospholipid, water and glucose all involved in the interaction rather than a competition between water and glucose for the phospholipid surface, as has been suggested in the literature.

Biological Transport↗
PubMed1987

Water vapor sorption of water-soluble substances: studies of crystalline solids below their critical relative humidities.

Water vapor sorption on unground and ground samples of sodium chloride and sodium salicylate at relative humidities below RHo, that at which deliquescence is initiated, has been measured. Sorption isotherms, expressed as the amount sorbed per unit area of solid surface, were different for unground and ground samples. Measurement of specific surface area for samples previously exposed to various relative humidities revealed no change with unground samples but a significant reduction with ground samples beyond about 20% relative humidity. Correcting isotherms for this change in area brings the results with ground and unground samples into closer agreement. These studies reveal that relatively low levels of water vapor sorption on crystalline water-soluble solids, below RHo, can give rise to some form of "surface dissolution" when the solid had been subjected to various forms of mechanical disturbance.

Absorption↗
PubMed1986

Adhesion of hydroxypropyl cellulose films to low energy solid substrates.

The adhesion of hydroxypropyl cellulose (HPC) to well-defined solid substrates was measured as a function of dry film thickness. A well-controlled butt adhesion test, providing a constant slow rate of film detachment, was used to keep the viscoelastic contribution of the film to the adhesion measurement constant. Films were cast or sprayed from solution in either triply distilled water or absolute ethanol onto relatively smooth surfaces of poly(methyl methacrylate), poly(ethylene terephthalate), and polyethylene. A linear relationship of increasing adhesion with decreasing dry film thickness was obtained for thin films (less than 20-microns thick) on all three surfaces. An adhesion value, A0, determined by extrapolating the adhesion data to zero film thickness, was shown to be proportional to the calculated thermodynamic work of adhesion, Wa, at the film-substrate interface. No significant effect of the method of film preparation, cast or sprayed, on the adhesion measurement was noted. Adhesion for a given film thickness was greater for films prepared from solutions having a higher initial polymer concentration or when using ethanol as opposed to water as the solvent.

Adhesiveness↗
PubMed1985

Moisture sorption kinetics for water-soluble substances. IV: Studies with mixtures of solids.

This paper extends earlier work from this laboratory concerning the sorption kinetics of water vapor on deliquescent water-soluble substances to mixtures of these solids. A theoretical model, based on heat transport control, excellently predicted a priori the rate of water uptake by a variety of binary mixtures of alkali halides and sugars. The rates for mixtures containing highly water-soluble quaternary ammonium salts, as either one or both of the components, were less successfully predicted as the combined water solubilities of the two components increased. It is concluded that water-soluble deliquescent substances, normally encountered in pharmaceutical dosage forms, rapidly form saturated aqueous solutions in the aqueous film formed as water vapor uptake proceeds, and that the water uptake rate can be predicted a priori from known and experimentally determinable parameters using the heat transport model.

Adsorption↗
PubMed1983

Moisture sorption kinetics for water-soluble substances. I: Theoretical considerations of heat transport control.

A model based on heat transport control was developed to describe the uptake of water on a deliquescent solid in an atmosphere of pure water vapor. The model assumes the presence of a saturated liquid film on the surface of the solid. The decrease in the vapor pressure of water over the surface, brought about by the colligative effect of solid dissolved in the liquid film, is effectively offset by the increase in temperature of the film (and the solid) caused by the heat released on condensation of the water vapor. The thermal transients die out quickly and a steady-state analysis is valid. At steady state the temperature of the liquid film (and solid) is that temperature at which the vapor pressure of water above the saturated solution is equal to the chamber pressure. Consequently, water uptake occurs at a rate that depends on the heat flux away from the surface. The water uptake rate, W'h, is constant at a given relative humidity and is described by an equation of the form W'h = (C + F) . ln (RHi/RHo), where C and F are conductive and radiative coefficients, RHi the chamber relative humidity, and RHo the relative humidity at and above which continuous water uptake (deliquescence) occurs. The model contains no adjustable parameters and can thus be directly tested against experimental results.

Absorption↗
PubMed1983

Moisture sorption kinetics for water-soluble substances. II: Experimental verification of heat transport control.

The rates of water sorption as a function of relative humidity for water-soluble substances exhibiting deliquescence have been measured in an atmosphere of pure water vapor. The substances studied included a series of alkali halides, choline halides, and sugars. The results were compared with a theoretical model, previously described, which relates the rate of water uptake to the transport of heat produced during the process away from the surface. Taking into account the heat of water vapor condensation, heat of solution, and heat of hydration, when hydration occurs, the model allows excellent a priori prediction of water uptake rates as a function of relative humidity.

Absorption↗
PubMed1983

Moisture sorption kinetics for water-soluble substances. III: Theoretical and experimental studies in air.

As an extension of the model of heat transport control developed for the kinetics of water sorption by water-soluble substances from an atmosphere of pure water vapor, equations have been developed to account for limitations of diffusion on mass transport of water vapor when air is present. Although the inability to determine the vapor diffusion layer thickness prevents using these equations to predict sorption behavior a priori, minimum water sorption rates can be calculated by assuming a diffusion layer thickness equal to the sample chamber radius. Combining heat transport and mass transport produces equations which describe very well the observed sorption by three water-soluble salts in one atmosphere of air. As in the absence of air, sorption rates are predicted and observed to be constant at a given atmospheric relative humidity.

Absorption↗