RESUMO
Bone grafting is crucial for bone regeneration. Recent studies have proposed the use of calcium citrate (CC) as a potential graft material. Notably, citrate does not inhibit hydroxyapatite (HAp) formation at specific calcium-to-citrate molar ratios. Octacalcium phosphate (OCP)/gelatine (Gel) composites, which are commonly produced from porcine Gel, are valued for their biodegradability and bone replacement capability. This study introduces fish Gel as an alternative to porcine Gel because of its wide acceptance and eco-friendliness. This is the first study to examine the interaction effects between two osteogenic materials, OCP/CC, and the influence of different gelatine matrix components on HAp formation in an SBF. Samples with varying CC contents were immersed in an SBF for 7 d and analysed using various techniques, confirming that high CC doses prevent HAp formation, whereas lower doses facilitate it. Notably, small-sized OCP/CC/porcine Gel composites exhibit a high HAp generation rate. Porcine Gel composites form denser HAp clusters, whereas fish Gel composites form larger spherical HAps. This suggests that lower CC doses not only avoid inhibiting HAp formation but also enhance it with the OCP/Gel composite. Compared with porcine Gel, fish Gel composites show less nucleation but an increased crystal growth for HAp.
Assuntos
Regeneração Óssea , Citrato de Cálcio , Durapatita , Gelatina , Durapatita/química , Gelatina/química , Regeneração Óssea/efeitos dos fármacos , Animais , Suínos , Citrato de Cálcio/química , Líquidos Corporais/química , Líquidos Corporais/metabolismo , Fosfatos de Cálcio/química , Substitutos Ósseos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines-HCT116 and SW620. 2c and 3c which are the derivatives containing o-hydroxyphenyl substituents exhibited the highest activity with IC50 against both cell lines in the range of 20-27 µM, which is comparable to the IC50 of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative 2a. Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, "CaCit-2a NPs" were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of 2a from the synthesised CaCit-2a NPs is pH-responsive, and 2a could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.
Assuntos
Antineoplásicos/farmacologia , Biguanidas/química , Citrato de Cálcio/química , Nanopartículas/química , Triazinas/síntese química , Triazinas/farmacologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Humanos , Nanopartículas/ultraestrutura , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Triazinas/químicaAssuntos
Cimentos Ósseos/química , Citrato de Cálcio/química , Sulfato de Cálcio/química , Colecalciferol/química , Teste de Materiais , Animais , Células da Medula Óssea/citologia , Cálcio/metabolismo , Proliferação de Células , Força Compressiva , Materiais Dentários , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Módulo de Elasticidade , Humanos , Concentração de Íons de Hidrogênio , Cinética , Camundongos , Microscopia Eletrônica de Varredura , Estresse Mecânico , Células Estromais/citologia , Propriedades de Superfície , Difração de Raios XRESUMO
Alkali supplements are used to treat calcium kidney stones owing to their ability to increase urine citrate excretion which lowers stone risk by inhibiting crystallization and complexing calcium. However, alkali increases urine pH, which may reduce effectiveness for patients with calcium phosphate stones and alkaline urine. Hydroxycitrate is a structural analog of citrate, widely available as an over-the-counter supplement for weight reduction. In vitro studies show hydroxycitrate has the capacity to complex calcium equivalent to that of citrate and that it is an effective inhibitor of calcium oxalate monohydrate crystallization. In fact, hydroxycitrate was shown to dissolve calcium oxalate crystals in supersaturated solution in vitro. Hydroxycitrate is not known to be metabolized by humans, so it would not be expected to alter urine pH, as opposed to citrate therapy. Preliminary studies have shown orally ingested hydroxycitrate is excreted in urine, making it an excellent candidate as a stone therapeutic. In this article, we detail the crystal inhibition activity of hydroxycitrate, review the current knowledge of hydroxycitrate use in humans, and identify gaps in knowledge that require appropriate research studies before hydroxycitrate can be recommended as a therapy for kidney stones.
Assuntos
Citrato de Cálcio/metabolismo , Citratos/administração & dosagem , Suplementos Nutricionais , Cálculos Renais/dietoterapia , Citrato de Cálcio/química , Humanos , Cálculos Renais/química , Cálculos Renais/urina , Eliminação Renal/efeitos dos fármacosRESUMO
When dairy powders are produced, the mineral fraction undergoes strong modifications during the vacuum concentration step, leading to the fouling of falling film evaporators. The objective of this study was to determine the nature of the deposits formed during the vacuum concentration of two fouling and highly mineralized products: hydrochloric acid whey and lactic acid whey. These products mainly differ in terms of their mineral composition: lactic acid whey contains a high level of lactic acid and traces of citrate, whereas hydrochloric acid whey contains citrate and no lactic acid. Concentrates at different concentration factors were produced using a pilot-scale falling film evaporator. The compositions of the fouling deposits as well as the precipitates present in the concentrates were deduced from the analytical determination of the composition of the concentrates and their respective diffusible phases. The behavior of the mineral fraction of both acid wheys during concentration was shown to be very different. In the case of hydrochloric acid whey, experimental results suggested a deposition of calcium and citrate ions in the evaporator as well as their precipitation in the highly concentrated products. On the contrary, neither mineral deposition nor precipitation occurred during the concentration of lactic acid whey. This study underlined the key role of citrate ions in the fouling of evaporators during the concentration of hydrochloric acid wheys.
Assuntos
Citrato de Cálcio/química , Impulso (Psicologia) , Ácido Clorídrico/química , Soro do Leite/química , Concentração de Íons de Hidrogênio , Ácido Láctico , Minerais , Nitrogênio/análise , VácuoRESUMO
BACKGROUND: There are many calcium supplements available in the market, especially those containing calcium in the form of carbonate, which unfortunately is not absorbed by the body to a sufficient degree. METHOD: Therefore, an attempt was made to prepare new sources of calcium, consuming the chicken eggshells as natural raw materials, which were used in preparation of tablets containing calcium carbonate and calcium citrate as well as tablets with calcium carbonate and calcium bisglycinate. The influence of raw material properties on the pharmaceutical availability of calcium from the obtained tablets was investigated. RESULTS: Based on the obtained calcium release profiles from the prepared tablets, it was found that the optimal source of calcium is a preparation containing calcium from chicken eggshells. It was found that both chicken eggshells and calcium bisglycinate (chelate) may be new, prospective sources of calcium. Calcium citrate prepared using eggshells as starting materials and bisglycinate is completely released within no more than 150 minutes. CONCLUSION: In turn, calcium carbonate added to calcium bisglycinate statistically significantly prolonges the release of calcium ions to 4 hours.
Assuntos
Cálcio/química , Cálcio/isolamento & purificação , Quelantes/química , Quelantes/isolamento & purificação , Casca de Ovo/química , Animais , Carbonato de Cálcio/química , Carbonato de Cálcio/isolamento & purificação , Citrato de Cálcio/química , Citrato de Cálcio/isolamento & purificação , Química Farmacêutica/métodos , Galinhas , Glicina/química , Glicina/isolamento & purificação , Compostos Organometálicos/química , Compostos Organometálicos/isolamento & purificação , Estudos Prospectivos , ComprimidosRESUMO
OBJECTIVES: Tricalcium citrate (TCC) was characterized as a tableting excipient for direct compression (DC) and dry granulation (DG). SIGNIFICANCE: Brittle materials usually lead to tablets of inferior mechanical strength compared to plastic deforming materials. A brittle material exhibiting a high tabletability with the ability to retain that behavior during recompression would represent a valuable alternative to the commonly used microcrystalline cellulose. METHODS: Tablets of TCC and other common fillers were directly compressed for the purpose of compression analysis including Heckel analysis, speed dependency, and lubricant sensitivity. DG by roller compaction of TCC was first simulated via briquetting and experiments were subsequently repeated on a roller compactor. RESULTS: TCC appears as an excellent flowing powder of large agglomerates consisting of lower micron to submicron platelets. Despite the brittle deformation mechanism identified in the Heckel analysis, TCC demonstrated a very high mechanical strength up to 11 MPa in conjunction with an astonishingly low solid fraction of 0.85 at a compression pressure of 400 MPa. This was seen along with hardly any speed and lubricant sensitivity. Nevertheless, disintegration time was very short. TCC tablets suffered only a little from the re-compression: a slight loss in tensile strength of 1-2 MPa was observed for granules produced via roller compaction. CONCLUSIONS: TCC was found to be suitable for DC as a predominantly brittle deforming filler, nevertheless demonstrating an enormous hardness yield while being independent of lubrication and tableting speed. TCC furthermore retained enough bonding capacity after DG to maintain this pronounced tabletability.
Assuntos
Citrato de Cálcio/química , Química Farmacêutica/métodos , Força Compressiva , Excipientes/química , Citrato de Cálcio/análise , Excipientes/análise , Dureza , Tamanho da Partícula , Resistência à TraçãoRESUMO
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 0.10â¯molâ¯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 8â¯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 0.10â¯molâ¯L-1 equimolar aqueous calcium chloride, sodium hydrogencitrate, and sodium hydrogenphosphate with pHâ¯5.5, and for 0.10â¯molâ¯L-1 equimolar aqueous calcium chloride, sodium hydrogencitrate, and sodium dihydrogenphosphate with pHâ¯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 5â¯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 pHâ¯5.5 and calcium hydrogencitrate complex dominating at pHâ¯4.1. Calcium hydrogencitrate is suggested to be the species involved in the crystal growth followed by solid state transformation to calcium citrate tetrahydrate.
Assuntos
Citrato de Cálcio/metabolismo , Fosfatos de Cálcio/metabolismo , Ácido Cítrico/metabolismo , Citrato de Cálcio/química , Fosfatos de Cálcio/química , Ácido Cítrico/químicaRESUMO
The anti-washout property, viscosity, and cytocompatibility to an osteoblastic cell line, MG-63, of anti-washout pastes were investigated. Mixing a hydroxyapatite/collagen bone-like nanocomposite (HAp/Col), an aqueous solution of sodium alginate (Na-Alg), which is a paste hardening and lubricant agent, and supplementation of calcium carbonate or calcium citrate (Ca-Cit) as a calcium resource for the hardening reaction realized an injectable bone paste. Adding Ca-Cit at a concentration greater than eight times the Ca2+ ion concentration to Na-Alg improved the anti-washout property. Although the viscosity test indicated a gradual increase in the paste viscosity as the calcium compounds increased, pastes with excess supplementation of calcium compounds exhibited injectability through a syringe with a 1.8 mm inner diameter, realizing an injectable bone filler. Furthermore, the anti-washout pastes with Ca-Cit had almost the same cell proliferation rate as that of the HAp/Col dense body. Therefore, HAp/Col injectable anti-washout pastes composed of the HAp/Col, Na-Alg, and Ca-Cit are potential candidates for bioresorbable bone filler pastes.
Assuntos
Materiais Biocompatíveis/química , Substitutos Ósseos/química , Cálcio/química , Colágeno/química , Durapatita/química , Alginatos/química , Cimentos Ósseos , Reabsorção Óssea , Osso e Ossos/metabolismo , Carbonato de Cálcio/química , Citrato de Cálcio/química , Linhagem Celular Tumoral , Proliferação de Células , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Íons , Teste de Materiais , Nanocompostos/química , Pós , ViscosidadeRESUMO
A convenient and effective soft chemical method is presented for the synthesis of nano-scaled calcium citrate sheets. The preparation involved the precipitation of nano-calcium citrate by adding ethanol to reach the super saturation state of a solution containing calcium and citrate salts. The obtained nano-calcium citrate formed nanosheets, with the following dimensions: width of about 50â¼500 nm and thickness of about 8â¼30 nm. The results of the XRD analysis confirmed that the obtained sample is calcium citrate tetrahydrate, and the crystal degree decreased with an increase quantity of ethanol added. Animal experiments showed that the calcium citrate can promote the formation of new bone.
Assuntos
Substitutos Ósseos/química , Citrato de Cálcio/química , Nanoestruturas/química , Animais , Humanos , Modelos Animais , Modelos Teóricos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
In this work, the efficiency of bioinspired citrate-functionalized nanocrystalline apatites as nanocarriers for delivery of doxorubicin (DOXO) has been assessed. The nanoparticles were synthesized by thermal decomplexing of metastable calcium/citrate/phosphate solutions both in the absence (Ap) and in the presence (cAp) of carbonate ions. The presence of citrate and carbonate ions in the solution allowed us to tailor the size, shape, carbonate content, and surface chemistry of the nanoparticles. The drug-loading efficiency of the two types of apatite was evaluated by means of the adsorption isotherms, which were found to fit a Langmuir-Freundlich behavior. A model describing the interaction between apatite surface and DOXO is proposed from adsorption isotherms and ζ-potential measurements. DOXO is adsorbed as a dimer by means of a positively charged amino group that electrostatically interacts with negatively charged surface groups of nanoparticles. The drug-release profiles were explored at pHs 7.4 and 5.0, mimicking the physiological pH in the blood circulation and the more acidic pH in the endosome-lysosome intracellular compartment, respectively. After 7 days at pH 7.4, cAp-DOXO released around 42% less drug than Ap-DOXO. However, at acidic pH, both nanoassemblies released similar amounts of DOXO. In vitro assays analyzed by confocal microscopy showed that both drug-loaded apatites were internalized within GTL-16 human carcinoma cells and could release DOXO, which accumulated in the nucleus in short times and exerted cytotoxic activity with the same efficiency. cAp are thus expected to be a more promising nanocarrier for experiments in vivo, in situations where intravenous injection of nanoparticles are required to reach the targeted tumor, after circulating in the bloodstream.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Apatitas/química , Citrato de Cálcio/química , Carbonatos/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Nanopartículas/química , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Composição de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Cinética , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Eletricidade Estática , TermodinâmicaAssuntos
Compostos de Cálcio/administração & dosagem , Suplementos Nutricionais , Osteoporose/prevenção & controle , Cálcio/análise , Cálcio/farmacocinética , Carbonato de Cálcio/administração & dosagem , Carbonato de Cálcio/química , Citrato de Cálcio/administração & dosagem , Citrato de Cálcio/química , Compostos de Cálcio/química , HumanosRESUMO
El citrato de calcio y magnesio es una materia prima obtenida a partir de dolomítas. Como parte de la optimización del proceso tecnológico, se estudió a escala de banco la etapa de secado para predecir su comportamiento a escalas superiores. Los resultados de este estudio mostraron que a partir de las 7:30 h de secado la muestra alcanza un contenido de humedad por debajo del 5 por ciento. Por otro lado, se observó que en las primeras 6 h la cantidad de agua evaporada representa más del 85 por ciento de la cantidad total presente en la muestra. Se concluye que el proceso de secado es adecuado para garantizar que el citrato de calcio y magnesio tenga un contenido de humedad por debajo de lo exigido para materias primas de calidad farmacéutica.
Calcium and magnesium citrate is a raw material obtained from dolomite. As part of the optimization of technological process, we studied it at bench scale, the dry stage to predict its behavior at higher scales. Results of this study showed that from 7:30 hours, sample drying reaches a humidity content lower 5 percent. Besides, we noted that during the first 6 hours, quantity of evaporation water represents more than 85 percent of total quantity present in sample. We conclude that drying process is appropriate to guarantees that calcium and magnesium citrate has humidity content lower than that required for raw products of pharmaceutical quality.
Assuntos
Citrato de Cálcio/análise , Citrato de Cálcio/química , Magnésio/análiseRESUMO
The amount of calcium available for absorption is dependent, in part, on its sustained solubility in the gastrointestinal (GI) tract. Many calcium salts, which are the calcium sources in supplements and food, have pH-dependent solubility and may have limited availability in the small intestine, the major site of absorption. The equilibrium solubility of four calcium salts (calcium oxalate hydrate, calcium citrate tetrahydrate, calcium phosphate, calcium glycerophosphate) were determined at controlled pH values (7.5, 6.0, 4.5 and < or = 3.0) and in distilled water. The solubility of calcium carbonate was also measured at pH 7.5, 6.0 and 4.5 with two CO(2) environments (0.3 and 152 mmHg) above the solution. The precipitation profile of CaCO(3) was calculated using in-vivo data for bicarbonate and pH from literature and equilibrium calculations. As pH increased, the solubility of each calcium salt increased. However, in distilled water each salt produced a different pH, affecting its solubility value. Although calcium citrate does have a higher solubility than CaCO(3) in water, there is little difference when the pH is controlled at pH 7.5. The partial pressure of CO(2) also played a role in calcium carbonate solubility, depressing the solubility at pH 7.5. The calculations of soluble calcium resulted in profiles of available calcium, which agreed with previously published in-vivo data on absorbed calcium. The experimental data illustrate the impact of pH and CO(2) on the solubility of many calcium salts in the presence of bicarbonate secretions in the intestine. Calculated profiles using in-vivo calcium and bicarbonate concentrations demonstrate that large calcium doses may not further increase intestinal calcium absorption once the calcium carbonate solubility product has been reached.
Assuntos
Compostos de Cálcio/química , Dióxido de Carbono/metabolismo , Trato Gastrointestinal/metabolismo , Carbonato de Cálcio/química , Citrato de Cálcio/química , Oxalato de Cálcio/química , Fosfatos de Cálcio/química , Precipitação Química , Glicerofosfatos/química , Concentração de Íons de Hidrogênio , Absorção Intestinal , Pressão Parcial , SolubilidadeRESUMO
The purpose of this study was to evaluate the potential of a pectin formulation with in situ gelling properties for the oral sustained delivery of paracetamol (acetaminophen). The formulations consisted of dilute aqueous solutions (1% to 2% w/v) of low methoxy pectin containing calcium ions in complexed form, which on release in the acidic environment of the stomach caused gelation of the pectin. In vitro studies demonstrated diffusion-controlled release of paracetamol from the gels over a period of 6 h. A bioavailability of approximately 96% of that of a paracetamol solution could be achieved from gels containing an identical dose of drug formed in situ in the stomachs of rats, with appreciably lower peak plasma levels and a sustained release of drug over a period of at least 6 h.
Assuntos
Acetaminofen/química , Excipientes/química , Pectinas/química , Acetaminofen/administração & dosagem , Acetaminofen/farmacocinética , Administração Oral , Animais , Disponibilidade Biológica , Citrato de Cálcio/química , Química Farmacêutica , Preparações de Ação Retardada , Géis , Técnicas In Vitro , Masculino , Soluções Farmacêuticas , Ratos , Ratos Wistar , ÁguaRESUMO
Fundamental to the processes of decalcification of or adhesion to mineralized tissues is the molecular interaction of acids with hydroxyapatite. This study was undertaken to chemically analyze the interaction of 1 mono-, 2 di-, 1 tri-, and 2 polycarboxylic acids with hydroxyapatite in an attempt to elucidate the underlying mechanism. Maleic, citric, and lactic acid decalcified hydroxyapatite, in contrast to oxalic acid and the two polycarboxylic acids that were chemically bonded to hydroxyapatite. Solubility tests showed that the calcium salts of the former were very soluble, whereas those of the latter could hardly be dissolved in the respective acid solutions. Based on these data, an adhesion/decalcification concept was advanced that predicts that carboxylic acids, regardless of concentration/pH, either adhere to or decalcify hydroxyapatite, depending on the dissolution rate of the respective calcium salts in the acid solution. This contrasting behavior of organic acids most likely results from their differential structural conformations.
Assuntos
Ácidos Carboxílicos/química , Durapatita/química , Resinas Acrílicas , Adesividade , Adsorção , Cálcio/química , Citrato de Cálcio/química , Compostos de Cálcio/química , Oxalato de Cálcio/química , Ácido Cítrico/química , Solubilidade do Esmalte Dentário , Microanálise por Sonda Eletrônica , Cimentos de Ionômeros de Vidro/química , Concentração de Íons de Hidrogênio , Lactatos/química , Ácido Láctico/química , Maleatos/química , Ácido Oxálico/química , Espectrofotometria Atômica , Análise Espectral/métodos , Propriedades de Superfície , Desmineralização do Dente/induzido quimicamenteRESUMO
For the scaling-up achieved by the use of the method of wet microwave granulation based on calculations, there is a need for an exact mathematical description for the relationship between the dose of radiation and the resultant effect. By assessing the physical, physical-chemical, and chemical factors, we may conclude that, by the gross kinetic evaluation of the change in the enthalpy and the loss of humidity, there is a possible solution for the mathematical description of the single-step, single-pot granulation from the practical aspect of finding ways to scale-up. This paper overviews the experiments performed in a laboratory-size microwave vacuum granulator in testing two different granules with respect to composition and permittivity and presents the evaluation of the experimental data.
Assuntos
Composição de Medicamentos/métodos , Micro-Ondas , Modelos Químicos , Tecnologia Farmacêutica/métodos , Citrato de Cálcio/química , Indústria Farmacêutica/métodos , Entropia , Excipientes/química , Umidade , Cinética , Lactose/química , Tamanho da Partícula , Pós , Água/química , Difração de Raios XRESUMO
The characterization of poly(ethylene) glycol calcium citrate microspheres is described. The calcium content and content uniformity of microspheres, prepared at five concentrations ranging from 46.56 micrograms/g to 81.49 mg/g, were determined by spectroscopy. Under sink conditions first-order in vitro dissolution kinetics were observed. Granules containing approximately 80 mg Ca++/g PEG gave an in vitro calcium release over a 3-day period similar to that of a calcium hydroxide product, Pulpdent.