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Absorption, and effect on gastric mucosa, of buffered and non-buffered tablets of acetylsalicylic acid.

The effect of buffered and non-buffered acetylsalicylic acid tablets on gastric mucosa and gastric distress was investigated in healthy volunteers and in patients with rheumatoid arthritis. The absorption of acetylsalicylic and salicylic acids was also measured. The absorption of salicylic acid was not affected in clinically significant amounts by buffering the tablets. Buffered tablets containing aluminum subacetate showed a slightly delayed absorption of salicylic acid. Damage to the gastric mucosa tended to be less after the preparation buffered by magnesium hydroxide. Subjective feelings to gastric distress were not affected by buffering.

Aspirin↗

Are buffers boring? Uniqueness and asymptotical stability of traveling wave fronts in the buffered bistable system.

Traveling waves of calcium are widely observed under the condition that the free cytosolic calcium is buffered. Thus it is of physiological interest to determine how buffers affect the properties of calcium waves. Here we summarise and extend previous results on the existence, uniqueness and stability of traveling wave solutions of the buffered bistable equation, which is the simplest possible model of the upstroke of a calcium wave. Taken together, the results show that immobile buffers do not change the existence, uniqueness or stability of the traveling wave, while mobile buffers can eliminate a traveling wave. However, if a wave exists in the latter case, it remains unique and stable.

Buffers↗

Comparison of peak shapes obtained with volatile (mass spectrometry-compatible) buffers and conventional buffers in reversed-phase high-performance liquid chromatography of bases on particulate and monolithic columns.

Retention factor, column efficiency and asymmetry factor were recorded for nine basic compounds on a number of RP-HPLC columns using phosphate and a variety of (MS-compatible) volatile mobile phase buffers of acid and neutral pH, in order to assess any effects of the buffer on performance. With formic or acetic acid, some phases gave partial or complete solute exclusion effects (reduced or negative k) compared with results using phosphate buffers at low pH. Despite its possible suppression of mass spectrometer sensitivity, trifluoroacetic acid was useful in enhancing retention times of relatively hydrophilic protonated bases, due to ion-pair effects. Peak shape was relatively poor on some pure silica-based ODS phases at pH 7 compared with results at acid pH. At low pH and at pH 7, ammonium and potassium phosphate gave very similar k, but the former may be preferable due to its volatile cation. Improved peak shapes, attributed to superior silanol masking effects, were obtained with ammonium phosphate at pH 7, but not at acid pH. Ammonium acetate gave acceptable peak shape at pH 7, but due to very limited buffer capacity, poor results were obtained for solutes having a pKa close to the mobile phase pH. Due to its instability, ammonium hydrogen carbonate is not a viable alternative buffer at pH 7.

Buffers↗

The effect of ionic strength on liposome-buffer and 1-octanol-buffer distribution coefficients.

The distribution of salmeterol and proxicromil between unilamellar vesicles of dioleoylphosphatidylcholine (DOPC) and aqueous buffer at pH 7.4 has been studied, using an ultrafiltration method, as a function of compound concentration, DOPC concentration, and buffer ionic strength. The binding of these ionized lipophilic compounds to neutral DOPC vesicles induces a surface charge, which causes the observed membrane distribution coefficient D(mem)obs to vary significantly with bound compound to DOPC ratio and with ionic strength. This variability is shown to be well-described with use of the Gouy-Chapman theory of the ionic double layer and is contrasted with the ideal behavior shown by the neutral compound clofibrate. Increasing ionic strength is also shown to increase the observed 1-octanol-buffer distribution coefficients D(o/w)obs of proxicromil but through a very different mechanism involving the extraction of ion pairs. This study highlights the experimental difficulty in determining concentration-independent liposome distribution coefficients of ionized lipophilic compounds and describes when deviations will be significant and how observed values may be corrected for such effects. The general effect of ionic strength on membrane-buffer distribution and 1-octanol-buffer distribution is discussed with particular reference to the very different propensity for ion pair formation shown by the two systems, and the most suitable experimental conditions that should be used with each system.

1-Butanol↗

Development of controlled-release SK&F 82526-J buffer bead formulations with tartaric acid as the buffer.

The purpose of this research was to design and develop a novel controlled-release bead formulation for oral administration with buffer crystals as a carrier for loading of fenoldopam mesylate, an intravenous antihypertensive agent, which provides an in vitro release rate of 30-50 mg/hr for 6-8 hr. Buffer crystals were coated in a fluid-bed granulator with a blend of gastrointestinal (GI) insoluble/enteric Eudragit polymers (such as RSPM/S100 polymer blend), drug was layered on these polymer-subcoated buffer beads by a slurry coating process, and the drug-layered beads were subsequently overcoated using a blend of GI insoluble/enteric polymers. The release of fenoldopam and tartaric acid was monitored by a two-stage dissolution procedure using USP Apparatus 2 (paddles at 50 rpm) and HPLC methodologies. The overcoating of drug-layered tartaric acid crystals with Eudragit polymers with different permeabilities significantly affected the release of fenoldopam. However, even the least permeable polymer, Eudragit RS, could not sustain the release of tartaric acid beyond 2 hr, suggesting the need to subcoat freely water-soluble tartaric acid crystals prior to drug layering. By varying the type/ratios of the GI insoluble/enteric polymers for subcoat and overcoat, capsule formulations were developed, which released fenoldopam and tartaric acid at different rates. The use of Eudragit polymer blends at the optimized ratios for both subcoat and overcoat resulted in a significant retardation in the release of tartaric acid; still, the tartaric acid release was faster than that of fenoldopam, suggesting the need to use a less water-soluble fumaric or succinic acid crystals as the buffer. However, the technology described using tartaric acid crystals as the buffer will be highly useful for weakly basic drug substances with less stringent pH-dependent solubility profiles.

Antihypertensive Agents↗

New aspects of buffering with multivalent weak acids in capillary zone electrophoresis: pros and cons of the phosphate buffer.

Phosphate buffer is frequently used as background electrolyte in capillary electrophoresis. It can cover a broad range of pH due to the three dissociation constants (pK1 = 2.0, pK2 = 7.2, and pK3 = 11.0) of phosphoric acid and because it is UV-light transparent. This contribution brings a theoretical study of the analytical separation performance (sample window, regions of peak symmetry, regions of fronting and tailing peaks) of phosphate buffer, serving as a model of buffering with multivalent weak acids. The study is based on the use of peak shape diagrams and covers the pH range 2.55-11.43. New important general knowledge has been revealed that single multivalent weak acids mimic the performance of background electrolytes with multiple coanionic species for anionic analyses. It is shown that simple phosphate buffers prepared by mixing phosphoric acid and potassium hydroxide may exhibit up to two regions of symmetry, of fronting as well as of tailing zones, on the mobility scale inside the sample window. Moreover they may exhibit a "schizophrenic" region of enormous electromigration dispersion.

Buffers↗

A family of high-buffering capacity diamino sulfate isoelectric buffers for pH-biased isoelectric trapping separations.

pH-biased isoelectric trapping separations are hindered by the lack of suitable isoelectric buffers with pI values in the 5.8 < pI range. Two generic approaches are described here for the cost-effective synthesis of a family of diamino sulfate buffers that have high buffering capacities in their isoelectric state: the first approach relies on the sulfation of existing, commercially available diamino alcohol intermediates, the second approach calls for the synthesis of diamino alcohols from epichlorohydrin and widely available secondary amines, and subsequent sulfation of the new diamino alcohol. The diamino sulfate buffers are recovered in isoelectric state, in high purity. Four members of the family having pI values in the 5.8 < pI < 8.9 range have been synthesized, analytically characterized by capillary electrophoresis (CE), electrospray ionization-time of flight-mass spectrometry (ESI-TOF-MS), 1-D and 2-D nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography. All four diamino sulfates have been successfully used as pH biasers in the receiving stream in preparative-scale pH-biased isoelectric trapping protein separations.

Buffers↗

Synthetic organic pH buffers can support fertilization of guinea pig eggs, but not as efficiently as bicarbonate buffer.

Bicarbonate ions (HCO3-) in the medium are not absolutely essential for the fertilization of guinea pig eggs. However, fertilization takes place most efficiently in HCO3- -buffered medium. Capacitation, the acrosome reaction, and zona penetration by spermatozoa can occur in HCO3- -free media with synthetic organic buffers (i.e., MOPS, TES, HEPES, Tris, and TAPSO) but not as efficiently as in the HCO3- -buffered medium. It appears that HCO3- functions as more than just a pH-buffering molecule.

Animals↗

Effect of buffer pH, buffer concentration and skin with or without enzyme inhibitors on the stability of [Arg(8)]-vasopressin.

The stability of [Arg(8)]-vasopressin (AVP) as a function of buffer pH, buffer concentration, salt concentration, temperature, and skin with and without enzyme inhibitors was investigated. AVP was analyzed by reverse-phase high-performance liquid chromatography. The results indicated that the buffer's pH affected the degradation rate of AVP. Buffer ions (H(2)PO(4)(-) and HPO(4)(2-)) and salt concentrations had no effect on the degradation of AVP. Maximum stability was achieved at pH 3.35 among pH values tested. The activation energy for the overall reaction was 21.5 kcal mol(-1) at pH 3.35. From the Arrhenius equation, the shelf-life of AVP at 25 degrees C and pH 3.35 was calculated to be 1.38 years. The degradation rate of AVP in the skin (area: 9 cm(2), thickness: 0.5 mm) was 0.22 h(-1). Bestatin (an aminopeptidase inhibitor) had the best stabilizing effect on the degradation of AVP by skin among the three enzyme inhibitors (i.e. aprotinin, bestatin, and leupeptin) studied. The degradation rate of AVP in the skin was reduced to 0. 059 h(-1) in the presence of bestatin in comparison with no inhibitor (0.22 h(-1)).

Animals↗

Semi-mechanistic partial buffer approach to modeling pH, the buffer properties, and the distribution of ionic species in complex solutions.

In many biological science and food processing applications, it is very important to control or modify pH. However, the complex, unknown composition of biological media and foods often limits the utility of purely theoretical approaches to modeling pH and calculating the distributions of ionizable species. This paper provides general formulas and efficient algorithms for predicting the pH, titration, ionic species concentrations, buffer capacity, and ionic strength of buffer solutions containing both defined and undefined components. A flexible, semi-mechanistic, partial buffering (SMPB) approach is presented that uses local polynomial regression to model the buffering influence of complex or undefined components in a solution, while identified components of known concentration are modeled using expressions based on extensions of the standard acid-base theory. The SMPB method is implemented in a freeware package, (pH)Tools, for use with Matlab. We validated the predictive accuracy of these methods by using strong acid titrations of cucumber slurries to predict the amount of a weak acid required to adjust pH to selected target values.

Algorithms↗

Comparison of three buffers used in the formulation of buffered charcoal yeast extract medium.

Growth of Legionella spp. on buffered charcoal yeast extract medium supplemented with alpha-ketoglutarate and formulated with 3-(n-morpholino)propanesulfonic acid (MOPS), 3-(n-morpholino)-2-hydroxypropanesulfonic acid (MOPSO), or n-(2-acetamido)-2-aminoethanesulfonic acid (ACES) buffer was similar. With three exceptions, growth was no different in buffered yeast extract broth supplemented with alpha-ketoglutarate and formulated with MOPS or ACES buffer.

Animals↗

Near-infrared spectroscopic assessment of mitochondrial oxygenation status--comparison during normothermic extracorporeal liver perfusion by buffer only or buffer fortified with washed red blood cells: an experimental study.

BACKGROUND: Use of marginal and non-heart-beating donors leads to an increased incidence of complications after clinical liver transplantation. Normothermic extracorporeal liver perfusion (NELP) may allow resuscitation and evaluation of such organs. Despite recent success in long-term liver preservation by NELP, no methods of organ evaluation have been defined. Mitochondrial cytochrome oxidase (Cyt Ox) levels reflect oxygen and substrate delivery, and hence ATP production at the cellular level. This study used near-infrared spectroscopy (NIRS) to measure Cyt Ox levels during NELP. METHODS: Livers retrieved from New Zealand white rabbits were immediately perfused in an extracorporeal circuit with oxygenated buffer (group A, n = 4) or red blood cell (RBC)-fortified buffer (group B, n = 4). Perfusion was continued for 3 hours at 37 degrees C pH 7.4, and perfusate was gassed with 95%O2/5%CO2 at 1 liter per minute. Cyt Ox levels were monitored continuously by NIRS and bile output was measured. RESULTS: Cyt Ox was reduced at the start of perfusion in both groups, but even more rapidly in the buffer-perfused group. After initial deterioration, Cyt Ox levels improved significantly (P < .05) with perfusion in the RBG-perfused group, but remained impaired in the buffer group 5.74 +/- 1.51 Deltamicromol/L and -25.77 +/- 21.94 Deltamicromol/L for groups B and A, respectively, at 180 minutes. Differences in bile output were not significant (19.33 +/- 9.50 and 25.00 +/- 16.81 micromol/min/100 g for groups B and A respectively). CONCLUSIONS: Cyt Ox levels may offer better viability markers than bile output. NIRS is a practical method to measure tissue oxygenation, and RBC-based perfusion provided better oxygenation during NELP.

Animals↗

New isoelectric buffers for capillary electrophoresis: N-carboxymethylated polyethyleneimine as a macromolecular isoelectric buffer.

Isoelectric buffers are attractive for electrophoresis because of their low conductivity, and their compatibility with indirect photometric detection in capillary electrophoresis (CE) where they do not interfere with the detection by exhibiting competitive displacement of the UV-absorbing probe ion. N-carboxymethylated polyethyleneimine (CMPEI) was prepared by introducing a half molar equivalent of carboxylate groups onto a polyethyleneimine backbone. Its isoelectric point determined by conductometric titration and from the pH of its dilute aqueous solution is approx. 6.8, which allows isoelectric buffering at a lower pH compared to histidine (pI7.7). Although the isoelectric point is somewhat diffuse, as expected for a polymeric compound, it exhibits a buffering capacity at a pI point of about twice that of histidine. Studies of electroosmotic flow (EOF) profile at various pH values in fused silica capillaries showed that CMPEI adsorbs onto the fused silica wall and reverses the EOF at pH < 6.5. CMPEI was applied as a buffer in an electrolyte containing 0.5 mM of the anionic dye tartrazine used as the probe for indirect detection of anions. The separation system exhibited a stable baseline, no system peaks, separation efficiencies of up to 195,000 theoretical plates, and detection limits down to 0.2 microM or 2 amol of injected analyte.

Journal Article↗

Sensitivity models in simulation of capillary zone electrophoresis: the effect of buffer power and initial buffer concentration.

Separation of proteins by capillary zone electrophoresis in an amphoteric medium is investigated by numerical simulation. We explain how sensitivity models can be used to gain further information about this process. The sensitivity models that are derived are used to study the sensitivity of the separation to the specific buffer capacity of the amphoteric molecule that serves as a buffer. The effect of changing the overall concentration of this ampholyte is also examined and it is shown that a change in its concentration is equivalent to a change in its buffer capacity.

Buffers↗

On the concept of "normalized buffering power/conductivity ratio" of isoelectric buffers for capillary zone electrophoresis.

The introduction of a new physico-chemical parameter is proposed: the "normalized buffering power/conductivity ratio". It expresses the ratio of buffering power to conductivity (Rbeta/lambda), normalized by the electrolyte concentration, and gives an opportunity to calculate the properties of buffering ions typically used in capillary electrophoretic separations of biopolymers. This procedure of normalization is possible due to the fact that, in the concentration range practically used, the relationship of Rbeta/lambda on concentration is close to linear.

Ampholyte Mixtures↗

Chloroplast thylakoid proteins associated with sequestered proton-buffering domains. Plastocyanin contributes buffering groups to localized proton domains.

Thylakoid membrane proteins are organized so as to shield 30-50 nmol H+ (mg Chl)-1 from freely equilibrating with either the external or the lumen aqueous phases. Amine groups provide binding sites for this metastable buffering array and can be quantitatively measured by acetylation using [3H]acetic anhydride. The principle of the assay is that a metastable acidic domain will have relatively less of the reactive neutral form of the amine compared to the amount present after addition of an uncoupler. The extent of the acetylation reaction is strongly influenced by whether the lumen pH comes to complete equilibrium with the external pH prior to adding the acetic anhydride. Determination of the lumen pH by [14C]methylamine distribution after the standard 3 or 5 min equilibration in pH 8.6 buffer indicated that the lumen may have been 0.2 to 0.3 pH more acidic than the external phase. This effect was taken into account by determining the pH dependence, in the pH 8.2-8.6 range, of acetylation of the membrane proteins studied, and the labeling data were conservatively corrected for this possible contribution. Experiments were carried out to identify the thylakoid proteins that contribute such metastable domain amine groups, using the above conservative correction. Surprisingly, plastocyanin contributes buried amine groups, but cytochrome f did not give evidence for such a contribution, if the conservative correction in the labeling was applied. If the correction was too conservative, cytochrome f may contribute amines to the sequestered domains. The new methodology verified earlier results suggesting that three Tris-releasable photosystem II-associated proteins also contribute significantly to the sequestered amine-buffering array.

Acetic Anhydrides↗

Formulation and some biological uses of a buffer mixture whose buffering capacity is relatively independent of pH in the range pH 4-9.

A mixture is described which has a buffering capacity which is essentially independent of pH in the range pH 4.0-9.0. It is shown how this buffer mixture may be used to determine the force-flux relationship of proton transfer between two aqueous phases separated by a phospholipid bilayer in vesicular systems and so demonstrate that this relationship is linear over a wide range of delta mu approximately H+. The buffer mixture can, furthermore, be employed to determine the volume enclosed within a vesicular preparation.

Buffers↗

High-performance chromatofocusing using linear and concave pH gradients formed with simple buffer mixtures. I. Effect of buffer composition on the gradient shape.

Numerical calculations together with simplified analytical relations based on local equilibrium theory are used to determine the factors which govern the shape of the gradient formed during chromatofocusing when simple mixtures of buffering species are employed to produce linear or concave pH gradients. The numerical and analytical development is also used to determine the relation between the gradient shape and the buffering capacities of the adsorbed and liquid phases. Experiments which verify the theoretical methods are described where internally generated, retained pH gradients of various shapes are formed using high-performance chromatography columns. The resulting experimental and theoretical basis can be employed as means for the selection of the buffer composition for use in chromatofocusing.

Buffers↗