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Biomedical subjects

S L Hem

Publications and source records attributed to S L Hem.

At least 55 records · Page 3Linked to original sources

Phosphate binding gels: balancing phosphate adsorption and aluminum toxicity.

The phosphate binding capacity of five commercial aluminum hydroxide phosphate-binding gels and two crystalline forms of aluminum hydroxide was studied by an in vitro procedure which simulated passage through the stomach to the small intestine. The potential for aluminum toxicity was estimated by determining the fraction of the dose which was converted into soluble aluminum species by acid neutralization at pH 3, 37 degrees C. The commercial products varied widely both in phosphate binding capacity and production of soluble aluminum species. The evidence suggests that the ideal phosphate binder will have a surface area small enough to minimize the formation of soluble aluminum species during the gastric residence time but also large enough to adsorb a clinically significant amount of phosphate.

Aluminum↗

Point of zero charge of amorphous aluminum hydroxide as a function of adsorbed carbonate.

The point of zero charge of 36 carbonate-containing aluminum hydroxide gels decreased with increased carbonate-to-aluminum molar ratio. Theoretical analysis supported this observation and showed that the point of zero charge was sensitive to low fractional coverage of surface sites by carbonate and that divalent carbonate is the predominant form of carbonate on the surface. The implications of the pH-point of zero charge relationship of aluminum hydroxide on the viscosity, adsorptive properties, rate of filtration, and removal of sodium are discussed.

Adsorption↗

Mechanism of freeze-thaw instability of aluminum hydroxycarbonate and magnesium hydroxide gels.

The effect of freeze-thaw cycles on the physical stability of aluminum hydroxycarbonate and magnesium hydroxide gels was studied. Coagulation following a freeze-thaw cycle, leading to the formation of visible aggregates, affected the content uniformity of both gels. The freeze-thaw cycles did not affect the crystal form or surface characteristics of the gels as determined by X-ray powder diffraction and point of zero charge, but caused a slight reduction in the rate of acid neutralization and a large increase in the rate of sedimentation. The greatest effect was observed after the first freeze-thaw cycle. While the duration of freezing was not a factor, the rate of freezing was important and was inversely related to the aggregate size. The aggregates which formed following a freeze-thaw cycle were not redispersed by shaking, but were reversed by ultrasonic treatment or homogenization. The adsorption of polymers or surface-active agents prior to freezing reduced and, in some cases, prevented the formation of aggregates. The physical instability produced by a freeze-thaw cycle was explained by the modified DLVO theory. The force exerted on the particles by the growing ice crystals forced the particles into the primary minimum, producing strong interparticle attraction. On thawing, simple agitation did not provide enough force to overcome the attractive force of the primary minimum. Adsorption of polymers or surface-active agents increased the steric repulsive force and prevented the particles from reaching the primary minimum.

Aluminum Hydroxide↗

Epimerization of benzylpenicilloic acid in alkaline media.

5R,6R-Benzylpenicilloic acid was found to epimerize slowly in alkaline media to 5S,6R-benzylpenicilloic acid until equilibrium was established. Epimerization proceeded via the imine tautomer of penamaldic acid rather than the enamine form and was found to favor the 5S,6R-epimer at equilibrium. The conversion process was monitored using both reverse-phase high-performance liquid chromatography and NMR spectroscopy.

Chemical Phenomena↗

Desorption of carbonate from aluminum hydroxycarbonate gel by nitrogen purging.

Carbonate was completely desorbed from amorphous aluminum hydroxycarbonate gel by purging with nitrogen. The reversibility of carbonate adsorption suggests that aluminum hydroxycarbonate particles are composed of planes of aluminum hydroxide with carbonate adsorbed at edge aluminum sites. A slow-reacting phase which was identified as a precursor of gibbsite, formed when the carbonate/aluminum molar ratio was less than 0.20.

Adsorption↗

Properties of carbonate-containing aluminum hydroxide produced by precipitation at constant pH.

Carbonate-containing aluminum hydroxide was precipitated at constant pH at intervals of 0.5 pH units from pH 6 to 10 by pumping 0.5 M AlCl3 into the reaction vessel at a constant rate of 2 mL/min and infusing 2 M Na2CO3 at a rate necessary to maintain the desired pH. The pH of precipitation affected both the particle size and the composition of the precipitate. The particle size of the precipitate decreased as the pH of precipitation was increased from 6 to 10. The precipitates formed between pH 7.5 and 9.5 contained crystalline sodium aluminum hydroxycarbonate (dawsonite) in addition to amorphous carbonate-containing aluminum hydroxide.

Aluminum Hydroxide↗

Exchange of sodium by magnesium in aluminum hydroxycarbonate gel.

Approximately 90% of the sodium present in a washed aluminum hydroxycarbonate gel was removed by exchange with magnesium. This behavior supports recent structural studies which have suggested that cations such as sodium serve as counterions in aluminum hydroxycarbonate gel. However, sodium could not be removed from dihydroxyaluminum sodium carbonate by exchange with magnesium because sodium is part of the crystal structure. It is hypothesized that aluminum hydroxycarbonate gels which resist removal of sodium are actually mixtures containing dihydroxyaluminum sodium carbonate in addition to aluminum hydroxycarbonate.

Aluminum Hydroxide↗

Adsorption of phosphate by aluminum hydroxycarbonate.

Phosphate is specifically adsorbed by aluminum hydroxycarbonate by anion ligand exchange. IR analysis indicated that phosphate exchanged with specifically adsorbed carbonate. Adsorption is favored by low pH and is inversely related to particle size. Adsorption of phosphate decreases the rate of acid neutralization of aluminum hydroxycarbonate. The results are applied to the treatment of hyperphosphatemia and hypophosphatemia.

Adsorption↗

Adsorption of pepsin by aluminum hydroxide I: Adsorption mechanism.

Adsorption of pepsin by gibbsite and boehmite, non-acid-reactive forms of aluminum hydroxide, was observed and related to the surface area of the adsorbent. Adsorption was pH dependent, with maximum adsorption occurring between pH 2.7-3.3 for gibbsite and pH 2.7-4.3 for boehmite. Electrostatic attraction was an important adsorption mechanism at the pH conditions encountered in the GI tract; the isoelectric point of pepsin was approximately 1, giving it a negative charge, and the point of zero charge for the adsorbents was greater than 9, giving them a positive charge. However, the pH-adsorption profile can not be fully explained by electrostatic considerations. Desorption studies indicate the importance of specific adsorption because pepsin was not desorbed by washing with acidified water, but was partly desorbed by exchange with phosphate. The IR spectrum of adsorbed pepsin also suggested that specific adsorption of pepsin occurred through anionic ligand exchange involving carboxylate groups of pepsin and surface aluminum ions.

Adsorption↗

Adsorption of pepsin by aluminum hydroxide II: Pepsin inactivation.

Pepsin adsorbed on gibbsite or boehmite, non-acid-reactive forms of aluminum hydroxide, had a significantly lower activity than pepsin in solution. IR and desorbed pepsin activity studies showed that the reduced activity of adsorbed pepsin was not due to denaturation of pepsin on adsorption. Steric occlusion of the active site, following pepsin adsorption, was responsible for the lower activity of pepsin adsorbed on gibbsite. The porous morphology of boehmite caused diffusional resistance and steric exclusion, contributing to the decreased activity of adsorbed pepsin. The specific inactivation of pepsin by adsorption on aluminum hydroxide may be important in ulcer therapy.

Adsorption↗

Convenient method of simultaneously analyzing aluminum and magnesium in pharmaceutical dosage forms using californium-252 thermal neutron activation.

A commercial antacid suspension containing aluminum hydroxide and magnesium hydroxide products was used as a model sample to study the use of a californium-252 thermal neutron activation as a method for quantifying aluminum content as well as for the simultaneous assay of aluminum and magnesium. A 3.5-micrograms californium-252 source was used for the activation, and the induced aluminum-28 and magnesium-27 activity was simultaneously measured by sodium iodide crystal gamma-ray spectrometry using dual single-channel analyzers and scalers. The antacid suspension was contained in a chamber designed with the unique capability of serving as the container for counting the induced radioactivity in addition to being the irradiation chamber itself. Ten replicate irradiations were performed, and the precision was compared with 10 replicate analyses of the antacid suspension using the official ethylenediaminetetraacetic acid titration method. For aluminum the precision was 1.4 versus 0.62% for the titration method. For the magnesium the precision was 5.3 versus 0.79% for the titration method. This pilot study demonstrated that use of more intense californium-252 sources, which are commonly available, would provide a method that is competitive with the ethylenediaminetetraacetic acid titration method in precision and in other aspects as well.

Aluminum↗

Stabilization of aluminum hydroxide gel by specifically adsorbed carbonate.

Ion-free aluminum hydroxide gel, prepared by the hydrolysis of aluminum tri-sec-butoxide, was observed by IR, X-ray analysis, and pH-stat titration to undergo rapid structural changes leading to the formation of pseudoboehmite and bayerite. The rate of development of order was directly related to the water-aluminum molar ratio. The Al--O bands at 625 and 470 cm-1 were the most sensitive indicators of the development of order in the gel structure. Direct evidence for the stabilizing effect of specifically adsorbed carbonate was obtained when carbon dioxide was introduced during the hydrolysis of aluminum tri-sec-butoxide. The resulting aluminum hydroxycarbonate gel possessed excellent antacid properties, retained its amorphous nature upon aging, and contained no cations other than aluminum. Hydrolysis of aluminum tri-sec-butoxide in the presence of stoichiometric amounts of sodium bicarbonate resulted in the immediate formation of crystalline sodium aluminum hydroxycarbonate (dawsonite).

Adsorption↗

Effect of surface charge and particle size on gel structure of aluminum hydroxycarbonate gel.

The effect of surface charge and particle size on the gel structure of aluminum hydroxycarbonate gel was studied through the use of a specially designed tension cell. Surface charge has a major effect on the coefficient of bulk compressibility. The charged state is more compressible at lower tensions while the neutral gel is more compressible at higher tensions. In addition, physical properties of gels having a small particle size are more profoundly influenced by interparticle forces than are gels consisting of larger particles. The effect of surface charge and particle size on gel structure is applied to physical properties such as viscosity and dewatering.

Aluminum Hydroxide↗

Effect of the pH-zero point of charge relationship on the interaction of ionic compounds and polyols with aluminum hydroxide gel.

The adsorption of magnesium nitrate, docusate sodium, and mannitol by chloride-containing aluminum hydroxide gel or aluminum hydroxycarbonate gel can be directly related to the surface charge characteristics of the aluminum hydroxide gel as determined by the pH-zero point of charge (ZPC) relationship. Magnesium cation is completely adsorbed under pH conditions where the gel has a negative surface charge, i.e. when the pH is above the ZPC. Docusate sodium is more strongly adsorbed when the pH-ZPC relationship causes the surface charge of aluminum when the pH-ZPC relationship causes the surface charge of aluminum hydroxycarbonate gel to be positive indicating adsorption of the docusate anion. However, adsorption also occurred when the pH was above the ZPC suggesting that adsorption of the hydrophobic portion of docusate anion by van der Waals forces also contributes to the overall adsorption mechanism. Mannitol is adsorbed under all pH conditions. However, greater adsorption occurs when the pH is above the ZPC. Maximum hydrogen bonding is believed to occur when mannitol acts as the proton donor and the negative aluminum hydroxycarbonate gel surface serves as the proton acceptor.

Adsorption↗

Separation of penicillin and its major degradation products by ion-pair reversed-phase high-pressure liquid chromatography.

An ion-pair reversed-phase high-pressure liquid chromatographic technique capable of separating penicillin and its major degradation products within 8 min was developed. The influence of pH, counterion concentration, buffer concentration, and organic modifier content was studied and the observed behavior of the compounds during the chromatographic process was discussed.

Chemical Phenomena↗

Formation of hydrotalcite in mixtures of aluminum hydroxycarbonate and magnesium hydroxide gels.

IR and X-ray analysis demonstrate that hydrotalcite forms during the aging of aluminum hydroxycarbonate gel and magnesium hydroxide gel mixtures. The formation of hydrotalcite produces a change in the pH-stat titrigram and a sharp increase in the pH of the mixture. Hydrotalcite was noted earlier in mixtures having a high molar ratio of magnesium to aluminum, a high total gel concentration, a high initial pH, or in mixtures stored at elevated temperatures. The addition of sorbitol to the mixtures substantially delayed the appearance of hydrotalcite. Nonacid-reactive hydrotalcite formed when mixtures of chloride-containing aluminum hydroxide gel and magnesium hydroxide gel were aged.

Aluminum Hydroxide↗