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This study aims to investigate key variables affecting the dissolution of amorphous pharmaceuticals. We examined sample treatment methods (centrifugation vs syringe filtration), time delays between sample collection and processing (immediate, 2, or 24 h), and different sample preparations (bare powder, capsules, or tablets). These factors were evaluated through both sink and nonsink dissolution experiments, using controlled supersaturation conditions (sink index ≈ 0.1) with amorphous solid dispersions (ASDs) containing low-substituted hydroxypropyl cellulose (L-HPC) and either indomethacin or posaconazole as model drugs. Our results highlighted the significant impact of syringe filtration on nonsink dissolutions, particularly the notable reduction in dissolved drug concentration, possibly due to filtration-induced precipitation. Moreover, introducing a delay of 2 or 24 h between sample collection and quantitation under nonsink conditions led to substantial concentration changes. This effect was not as pronounced when samples underwent centrifugation, and only the analysis was delayed for 2 h. The findings also emphasize the importance of accounting for delays introduced by pharmaceutical formulations, particularly in assessing the kinetic-solubility profiles of ASDs. This research offers valuable insights into the field of ASDs, enhancing our understanding of how these variables can influence dissolution results.

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Are surface nanobubbles transient or thermodynamically stable structures? This question remained controversial until recently, when the stability of gas nanobubbles at solid-liquid interfaces was demonstrated from thermodynamic arguments in closed systems, establishing that bubbles with radii of hundreds of nanometers can be stable at modest supersaturations if the gas amount is finite. Here we develop a grand-canonical description of bubble formation that predicts that nanobubbles can nucleate and remain thermodynamically stable in open boundaries at high supersaturations when pinned to hydrophobic supports as small as a few nanometers. While larger bubbles can also be stable at lower supersaturations, the corresponding barriers are orders of magnitude above kT, meaning that their formation cannot proceed via heterogeneous nucleation on a uniform solid interface but must follow some alternative path. Moreover, we conclude that a source of growth-limiting mechanism, such as pinning or gas availability, is necessary for the thermodynamic stabilization of surface bubbles.

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This study sought to develop polymer-lipid hybrid solid dispersions containing the poorly soluble drug lopinavir (LPV) by hot-melt extrusion (HME). Hence, the lipid and polymeric adjuvants were selected based on miscibility and compatibility studies. Film casting was used to assess the miscibility, whereas thermal, spectroscopic, and chromatographic analyses were employed to evaluate drug-excipient compatibility. Extrudates were obtained and characterized by physicochemical tests, including in vitro LPV dissolution. Preformulation studies led to select the most appropriate materials, i.e., the polymers PVPVA and Soluplus®, the plasticizers polyethylene glycol 400 and Kolliphor® HS15, phosphatidylcholine, and sodium taurodeoxycholate. HME processing did not result in LPV degradation and significantly increased entrapment efficiency (93.8% ± 2.8 for Soluplus® extrudate against 19.8% ± 0.5 of the respective physical mixture). LPV dissolution was also increased from the extrudates compared to the corresponding physical mixtures (p < 0.05). The dissolution improvement was considerably greater for the Soluplus®-based formulation (24.3 and 2.8-fold higher than pure LPV and PVPVA-based extrudate after 120 min, respectively), which can be attributed to the more pronounced effects of HME processing on the average size and LPV solid-state properties in the Soluplus® extrudates. Transmission electron microscopy and chemical microanalysis suggested that the polymer-lipid interactions in Soluplus®-based formulation depended on thermal processing.

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Amorphous solid dispersions (ASDs) based on water-insoluble hydrophilic polymers can sustain supersaturation in their kinetic solubility profiles (KSPs) compared to soluble carriers. However, in the limit of very high swelling capacity, the achievable extent of drug supersaturation has not been fully examined. This study explores the limiting supersaturation behavior of ASDs of poorly soluble indomethacin (IND) and posaconazole (PCZ) based on a high-swelling excipient, low-substituted hydroxypropyl cellulose (L-HPC). Using IND as a reference, we showed that the rapid initial supersaturation buildup in the KSP of IND ASD can be simulated through sequential IND infusion steps, however at large times the KSP of IND release from ASD appears more sustained than direct IND infusion. This has been attributed to potential trapping of seed crystals generated in the L-HPC gel matrix thus limiting their growth and rate of desupersaturation. Similar result is also expected in PCZ ASD. Furthermore, the current drug loading process for ASD preparation resulted in the agglomeration of L-HPC based ASD particles, producing granules of up to 300-500 µm (cf. 20 µm individual particle), with distinct kinetic solubility profiles. This feature makes L-HPC particularly suitable as ASD carriers for fine tuning of supersaturation to achieve enhanced bioavailability for poorly soluble drugs.

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A graphical analysis of both drug and coformer concentrations contributed by dissolving cocrystals is presented in the context of a simplified cocrystal phase diagram. The conceptual basis and analysis identify parameters that control cocrystal dissolution-drug supersaturation-precipitation (DSP) behavior. The important effects of coformer concentration, cocrystal dose, and cocrystal solubility on drug supersaturation levels are demonstrated and quantified by the DSPindex. While the studies presented rely on high and nonstoichiometric coformer concentrations contributed by the dissolving cocrystals, the concepts and findings can answer the question of whether and how much coformer should be added to cocrystal dissolution media or formulations.

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This study evaluated the ability of different sweeteners to improve dissolution and to form and stabilize supersaturated solutions of griseofulvin (GSF), comparing a eutectic mixture and amorphous formulations. Among the sweeteners tested, only saccharin (SAC) was able to delay drug precipitation in buffer (area under the curve (AUC) increase of 40%) and in fasted state simulated intestinal Fluid (FaSSIF, AUC increase of 20%) compared to pure media. GSF solubility was not affected by the presence of isomalt (ISO), maltitol (MALT) and SAC in buffer pH 6.5 but was reduced in FaSSIF. The quenched cooled amorphous formulation GSF-SAC QC -with the carrier that forms a eutectic mixture with GSF -provided higher drug release in buffer than amorphous formulations with ISO and MALT. In FaSSIF, SAC slightly changed the microenvironment's hydrophobicity (observed in fluorescence studies) and both its amorphous formulation (GSF-SAC QC) and its eutectic mixture (GSF-SAC EM) dissolved at concentrations above drug solubility, achieving supersaturation ratio (SR, Eq. (1)) of 4.14 and 3.15, respectively. The main finding of this study was that for the first time a eutectic mixture acted as a supersaturating drug delivery system, emphasizing the importance of investigating EMs during preformulation studies of fast-crystallizing poorly water-soluble drugs.

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The purpose of this study was to associate the poorly water-soluble antihypertensive drugs candesartan cilexetil (CC) and hydrochlorothiazide (HCTZ) as fixed-dose combination, in the form of ternary Amorphous Solid Dispersions (ASD), using hydroxypropylmethylcellulose acetate succinate (HPMCAS) type M as polymeric carrier. The potential of the system to generate and to maintain supersaturation of both drugs was also evaluated. The ASDs were prepared by ball milling technique and solid-state characterization was performed by differential scanning calorimetry (DSC), Fourier transformed infrared spectroscopy (FTIR) and X-ray powder diffraction (XRPD). Interaction between drugs and polymer in solid-state was evaluated by molecular metadynamics simulations. In vitro supersaturation profiles were determined in biorelevant medium. Physicochemical stability of ASDs was also evaluated under different storage conditions. Amorphization of both drugs was confirmed by solid-state characterization techniques. Molecular metadynamics simulations indicated that CC has stronger interaction with HMPCAS than HCTZ. In vitro supersaturation studies have shown that ternary ASDs could generate and maintain supersaturation of both drugs in biorelevant medium. The polymer reduced the desupersaturation of both drugs. Ternary ASDs also showed physicochemical stability over a period of 90 days, demonstrating the potential of the polymer in reducing the drugs recrystallization over the time. Ternary ASDs of CC, HCTZ and HPMCAS can be considered a promising system to associate the drugs as fixed-dose combinations. Also, these systems generate and maintain supersaturation of both drugs in biorelevant medium, with great storage stability. HPMCAS M was a good carrier for reducing the desupersaturation of associated HCTZ and CC.

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It has been reported that polysaccharides like carrageenan can change the crystallization of lactose. However, it is still unclear whether changes in lactose mutarotation, solubility, and super-solubility are involved in carrageenans' effect on lactose crystallization. It has been established that the conversion of α- to ß-lactose forms (mutarotation) in an aqueous solution has a significant impact on lactose crystallization. Similarly, lactose solubility changes lead to changes in the metastable zone (MZ), a region between the solubility and super-solubility of lactose. The width of this MZ determines the temperature drop necessary to induce lactose nucleation. This work aimed to study the effect of carrageenans on lactose mutarotation and solubility. For this purpose, lactose solutions were added with ι and κ- carrageenan at two concentrations: 50 and 100 mg L-1. Optical rotation measurements estimated the proportion of ß/α isomers in lactose solutions. Besides, solubility and super- solubility was determined to build the MZ. The presence of carrageenans changed both the time to reach the mutarotation balance and the proportion of ß/α isomers at mutarotation equilibrium. Carrageenans decreased the solubility of lactose in a range of temperatures between 10 and 60 °C and reduced the metastable zone width (MZW).

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Saturated solutions of calcium l-lactate in water or in deuterium oxide continuously dissolve calcium l-lactate by addition of solid sodium d-gluconate and become strongly supersaturated in calcium d-gluconate due to no or slow precipitation. The quantification of total dissolved calcium allied with the calcium complexes equilibrium constants allowed an ion speciation, which shows an initial non-thermal and spontaneous supersaturation of more than a factor of 50 at 25 °C only slowly decreasing after initiation of precipitation of calcium d-gluconate after a lag phase of several hours. A mathematical model is proposed, based on numerical solution of coupled differential equations of dynamics of l-lactate and d-gluconate exchange during the lag phase for precipitation and during precipitation. A slow exchange of l-lactate coordinated to calcium with d-gluconate is indicated with a time constant of 0.20 h-1 in water and of 0.15 h-1 in deuterium oxide and a kinetic deuterium/hydrogen isotope effect of 1.25. Such spontaneous non-thermal supersaturation and slow ligand exchange with a pseudo first order equilibration process with a half-life of 3.5 h in water for calcium hydroxycarboxylates can help to understand the higher calcium bioavailability from calcium hydroxycarboxylates compared to simple salts.

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Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=Cdose/Sdrug), cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug), and dissolution media affect cocrystal dissolution-drug supersaturation and precipitation (DSP) behavior. SA and Ksp values of 1:1 cocrystals of meloxicam-salicylic acid (MLX-SLC) and meloxicam-maleic acid (MLX-MLE) were determined at cocrystal/drug eutectic points. Results demonstrate that both cocrystals enhance SA by orders of magnitude (20 to 100 times for the SLC and over 300 times for the MLE cocrystal) in the pH range of 1.6 to 6.5. It is shown that during dissolution, cocrystals regulate the interfacial pH (pHint) to 1.6 for MLX-MLE and 4.5 for MLX-SLC, therefore diminishing the cocrystal dissolution rate dependence on bulk pH. Do values ranged from 2 (pH 6.5) to 410 (pH 1.6) and were mostly determined by the drug solubility dependence on pH. Drug release profiles show that maximum supersaturation (σmax=Cmax/Sdrug)and AUC increased with increasing Do as pH decreased. When Do>>SA, the cocrystal solubility is not sufficient to dissolve the dose so that a dissolution-precipitation quasi-equilibrium state is able to sustain supersaturation for the extent of the experiment (24 h). When Do<

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Candesartan cilexetil (CC) is a poorly soluble antihypertensive drug with in vivo absorption limited by its low aqueous solubility. Aiming to generate CC supersaturation as strategy to improve its absorption and bioavailability, amorphous solid dispersions (ASDs) of CC with hydroxypropylmethylcellulose acetate succinate type M (HPMCAS M) were developed and evaluated by in vitro and in vivo techniques. The ASDs were characterized by several solid-state techniques and evaluated regarding the supersaturation generation and maintenance under non-sink conditions in biorelevant medium. Stability studies at different storage conditions and in vivo pharmacodynamics studies were performed for the best formulation. The ASD developed presented appropriate drug amorphization, confirmed by solid state characterization, and CC apparent solubility increases around 85 times when compared to the pure crystalline drug. Supersaturation was maintained for up to 24 h in biorelevant medium. The in vivo pharmacodynamics studies revealed that ASD of CC with the polymer HPMCAS M presented an onset of action about four times faster when compared to the pure crystalline drug. The CC-HPMCAS ASD were successfully developed and demonstrated good physical stability under different storage conditions as well as promising results that indicated the ASD potential for improvement of CC biopharmaceutical properties.

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Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) is a solubilizing copolymer commonly applied as carrier in solid dispersions of poorly soluble drugs. This polymer is used to increase the apparent solubility of drugs with low aqueous solubility and consequently enhance drug absorption by the human gastrointestinal tract. To select the appropriate carrier to compose solid dispersions, in vitro supersaturation studies were applied as a pre-formulation tool, using different dissolution media. During in vitro supersaturation studies performed for the poorly soluble drug candesartan cilexetil, it was found that Soluplus® may interact with components of the biorelevant medium Fasted State Simulated Intestinal Fluid, lowering the drug apparent solubility. Dynamic Light Scattering and Transmission Electron Microscopy analyses were performed, as well as fluorescence measurements, aiming to characterize the interaction behavior and determine the polarity of the microenvironment. It was evidenced that Soluplus® interacted preferentially with lecithin, forming mixed micelles with a more polar microenvironment, which lowered the candesartan cilexetil solubilization capacity and consequently reduced its apparent solubility in the biorelevant medium. These findings are important to emphasize the key role of the media selection for in vitro solubility-supersaturation studies, where media that could mimic the human gastrointestinal environment are recommended.

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Griseofulvin (GSF) is an antifungal drug that has low aqueous solubility and low oral bioavailability. Amorphous systems are capable to promote rapid drug dissolution, usually affording concentrations above drug solubility in the gastrointestinal tract (supersaturation) in order to promote better absorption. Thus, the aim of this work was to evaluate the ability of amino acids, as hydrophilic carriers, to improve drug kinetic solubilization and to stabilize GSF supersaturated solutions, as well as to stabilize GSF amorphous systems at solid-state. The effect of 5 amino acids on GSF precipitation behavior was investigated by solvent shift method. Amorphous systems were developed by ball milling (GSF + amino acid 1:1 M ratio) and Quench Cooling (to obtain GSF QC) techniques. The samples were characterized by solid-state techniques, submitted to in vitro kinetic solubility studies and evaluated under stability tests. Aspartic acid, methionine, valine and tryptophan demonstrated similar anti-precipitant abilities in phosphate buffer pH 6.5. However, in FaSSIF biorelevant medium, tryptophan was only one able to slow down the drug precipitation. The characterization of milled samples showed that an amorphous system was obtained just using the combination of the drug with tryptophan (GSF-TRYP BM). At the higher dose tested (0.850 mmol L-1) during in vitro kinetic solubility studies, this amorphous system increased the AUC in FaSSGF (88.6%) and FaSSIF (58.2%) media when compared to GSF QC. Thus, the ability of this amino acid to inhibit GSF precipitation appears to be dependent on its concentration in solution and could be optimized. During the stability study, TRYP inhibited GSF recrystallization in the solid-state for a period of 12 months, whereas GSF QC recrystallized in 1 week.

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Background: The drug supersaturation in the intestinal lumen for few hours could result in high bioavailability. The goal of this study was the development of a supersaturating drug delivery system containing sulfamethoxazole and trimethoprim at fixed dose combination (sulfamethoxazole:trimethoprim 5:1 w/w). Methods: The amorphous solid dispersions were formed at three different proportions containing 30, 50 and 70% of Eudragit EPO in the formulation. Results: The supersaturation state is formed by the amorphous drugs produced by spray drying technique, and the maintenance of this state is due to the chemical interactions between the drugs and the polymer selected, which was observed in the fluorescence interaction studies realized between the drugs and the polymer. The Formulation containing 70% of the polymer was able to produce and maintain the supersaturated state of both drugs for 24 h. Solid state characterization demonstrated the amorphization of the drugs in the solid dispersion and indicated the hydrogen bond formation responsible for the improvement in the apparent solubility. This formulation presented an improved antibacterial activity when compared to the combination of the drugs. Conclusion: For the first time, a supersaturating drug delivery system was developed to the complementary antibacterial drugs. This ternary formulation is a powerful alternative to improve oral absorption of recognized safety drugs, reducing the dose and consequently the antibiotic resistance emergence.

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Nhecolândia is a vast sub-region of the Pantanal wetland in Brazil with great diversity in surface water chemistry evolving in a sodic alkaline pathway under the influence of evaporation. In this region, >15,000 shallow lakes are likely to contribute an enormous quantity of greenhouse gas to the atmosphere, but the diversity of the biogeochemical scenarios and their variability in time and space is a major challenge to estimate the regional contribution. From 4 selected alkaline lakes, we compiled measurements of the physico-chemical characteristics of water and sediments, gas fluxes in floating chambers, and sedimentation rates to illustrate this diversity. Although these lakes have a similar chemical composition, the results confirm a difference between the black-water and green-water alkaline lakes, corresponding to distinct biogeochemical functioning. This difference does not appear to affect lake sedimentation rates, but is reflected in gas emissions. Black-water lakes are CO2 and CH4 sources, with fairly constant emissions throughout the seasons. Annual carbon dioxide and methane emissions approach 0.86molm-2y-1 and 0.07molm-2y-1, respectively, and no clear trend towards N2O capture or emission was observed. By contrast, green-water lakes are CO2 and N2O sinks but important CH4 sources with fluxes varying significantly throughout the seasons, depending on the magnitude of the phytoplankton bloom. The results highlight important daily and seasonal variations in gas fluxes, and in particular a hot moments for methane emissions, when the O2-supersaturation is reached during the afternoon under extreme bloom and sunny weather conditions, provoking an abrupt O2 purging of the lakes. Taking into account the seasonal variability, annual methane emissions are around 10.2molm-2y-1, i.e., much higher than reported in previous studies for alkaline lakes in Nhecolândia. Carbon dioxide and nitrous oxide consumption is estimated about 1.9molm-2y-1 and 0.73mmolm-2y-1, respectively. However, these balances must be better constrained with systematic and targeted measurements throughout the seasons.

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Dissolution of amorphous calcium phosphate (ACP) in aqueous citrate at varying pH has been studied with perspective of increasing availability of calcium from sidestreams of whey protein, lactose and/or cheese production or on development of new functional foods. ACP formed as an initial precipitate in 0.10 mol L-1 equimolar aqueous calcium chloride, sodium citrate, and sodium hydrogenphosphate was used as model for mineral residues formed during milk processing. Upon acidification of the ACP suspension by hydrochloric acid decreasing pH from 6.5 to 4.5, the transformations of ACP occurred through an 8 h period of supersaturation prior to a slow precipitation of calcium citrate tetrahydrate. This robust supersaturation, which may explain increased availability of calcium phosphates in presence of citrate, presented a degree of supersaturation of 7.1 and was characterized by precipitation rates for 0.10 mol L-1 equimolar aqueous calcium chloride, sodium hydrogencitrate, and sodium hydrogenphosphate with pH 5.5, and for 0.10 mol L-1 equimolar aqueous calcium chloride, sodium hydrogencitrate, and sodium dihydrogenphosphate with pH 4.1, with a degree of supersaturation of 2.7. The crystallization processes were similar according to Avrami's model with a half-life for precipitation of approximately 5 h independent of the degree of supersaturation. Ion speciation based on measurement of pH, and total concentrations of calcium, phosphate and citrate, and of conductivity and calcium ion activity during precipitation indicates a low driving force for precipitation with calcium citrate complex dominating at pH 5.5 and calcium hydrogencitrate complex dominating at pH 4.1. Calcium hydrogencitrate is suggested to be the species involved in the crystal growth followed by solid state transformation to calcium citrate tetrahydrate.

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Among the strategies to improve the biopharmaceutic properties of poorly soluble drugs, Supersaturating Drug Delivery Systems like polymer-based amorphous solid dispersions (SD) have been successfully applied. The screening of appropriate polymeric carriers to compose SD is a crucial point on their development. In this study, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS) types L, M and H and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL) were evaluated by in vitro supersaturation studies regarding their anti-precipitant ability on the poorly soluble drug candesartan cilexetil (CC) under two different media, including biorelevant conditions. According to the results, HPMCAS M was considered the best carrier to develop SD containing CC among all the polymers tested, due to its good anti-precipitant performance in both media. In addition, the medium used in the in vitro supersaturation studies played an important role on the results, and its selection should be carefully done.

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Supersaturating drug delivery systems (SDDS), as solid dispersions (SDs), stand out among strategies to enhance bioavailability of poorly soluble drugs. After oral administration, their dissolution in gastrointestinal fluids often leads to supersaturation, which drives to a rapid and sustained absorption. Polymers and surfactants play important roles in SDs through inhibiting precipitation caused by transitions from amorphous into crystalline form, in supersaturated solutions, and also through improving SDs physical stability. Novel chlorthalidone SDs, a BCS IV drug, were developed using polymeric and non-polymeric carriers, specially a polymer-surfactant complex. SDs drug releases were evaluated using sink and non-sink conditions in water and biorelevant medium. Their physical stability was also monitored under different storage conditions. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL), sodium lauryl sulfate (SLS) and a combination of both showed promising results in apparent solubility studies, and therefore they were selected to compose the spray dried SDs. Dissolution studies demonstrated the SOL-SLS complex potential for providing chlorthalidone fast release (>80% in 15min), producing and maintaining in vitro supersaturation. This formulation comprising high drug loading (75%) reached a high supersaturation degree under non-sink condition (up to 6-fold the equilibrium solubility) once maintained for 6h in biorelevant medium. In addition, this SD presented better physical stability when compared to the chlorthalidone neat amorphous. The SOL-SLS complex impacts positively on chlorthalidone release and physical stability, highlighting its potential as carrier in SDDS of a poorly soluble drug.

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A formação de urólitos no trato urinário é problema clínico significativo para animais de companhia.Sabe-se que a dieta influencia a composição da urina, de modo que determinados fatores alimentares,como a composição mineral, desempenham papel significativo no aumento do risco ou na prevenção deurolitíases. Altas concentrações de soluto, com subseqüente supersaturação da urina podem favorecera formação de cristais e cálculos. O pH urinário influencia a solubilidade dos minerais e conseqüenteformação de cristais. Urólitos de estruvita e oxalato de cálcio são os tipos mais comumente encontradosem gatos, sendo a estruvita associada a um pH urinário alcalino e o oxalato de cálcio a um pH urinárioácido. Um método prático para se predizer o efeito de um alimento sobre o pH urinário é pelo cálculodo excesso de bases (EB). O EB da dieta é definido como a diferença em miliequivalentes (mEq) entre osprincipais cátions e ânions e pode ser calculado a partir de várias equações propostas. O EB da dieta tornapossível a descrição de inúmeros efeitos importantes do alimento sobre o balanço ácido-básico orgânico

The formation of uroliths in the urinary tract is a significant clinical problem for pets. It is known thatdiet influences the composition of urine, so that certain dietary factors, such as mineral composition,play a significant role in increasing the risk or prevention of urolithiasis. High concentrations of solute,with subsequent supersaturation of urine can promote the formation of crystals and stones. UrinarypH influences the solubility of minerals and consequent formation of crystals. Struvite uroliths andcalcium oxalate are the most commonly types found in cats, being struvite associated with an alkalineand calcium oxalate to an acid urinary pH. A practical method for predicting the effect of food onurinary pH is the calculation of base excess (BE). Diet´s BE is defined as the difference in milliequivalents(mEq) between major cations and anions and can be calculated from several equations. Diet´sBE makes possible the description of many important effects of food on the organic acid-base balance

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A formação de urólitos no trato urinário é problema clínico significativo para animais de companhia.Sabe-se que a dieta influencia a composição da urina, de modo que determinados fatores alimentares,como a composição mineral, desempenham papel significativo no aumento do risco ou na prevenção deurolitíases. Altas concentrações de soluto, com subseqüente supersaturação da urina podem favorecera formação de cristais e cálculos. O pH urinário influencia a solubilidade dos minerais e conseqüenteformação de cristais. Urólitos de estruvita e oxalato de cálcio são os tipos mais comumente encontradosem gatos, sendo a estruvita associada a um pH urinário alcalino e o oxalato de cálcio a um pH urinárioácido. Um método prático para se predizer o efeito de um alimento sobre o pH urinário é pelo cálculodo excesso de bases (EB). O EB da dieta é definido como a diferença em miliequivalentes (mEq) entre osprincipais cátions e ânions e pode ser calculado a partir de várias equações propostas. O EB da dieta tornapossível a descrição de inúmeros efeitos importantes do alimento sobre o balanço ácido-básico orgânico(AU)

The formation of uroliths in the urinary tract is a significant clinical problem for pets. It is known thatdiet influences the composition of urine, so that certain dietary factors, such as mineral composition,play a significant role in increasing the risk or prevention of urolithiasis. High concentrations of solute,with subsequent supersaturation of urine can promote the formation of crystals and stones. UrinarypH influences the solubility of minerals and consequent formation of crystals. Struvite uroliths andcalcium oxalate are the most commonly types found in cats, being struvite associated with an alkalineand calcium oxalate to an acid urinary pH. A practical method for predicting the effect of food onurinary pH is the calculation of base excess (BE). Diet´s BE is defined as the difference in milliequivalents(mEq) between major cations and anions and can be calculated from several equations. Diet´sBE makes possible the description of many important effects of food on the organic acid-base balance(AU)

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