Citric Acid Crystals Research Articles

Growth Kinetics of Anhydrous Citric Acid Under Optimized Conditions in a Vibrated Batch Crystallizer

Objective: The aim of this paper is to investigate the crystallization of citric acid on a vibrated bed within a stainless-steel crystallizer, featuring a jacket and a trunk-conical shape, utilizing a constrained quantity of seed crystals. Theoretical Framework: This study assessed mass yield and characteristic dimensions in the crystallization of anhydrous citric acid using a vibrated bed batch crystallizer, employing a limited quantity of seed crystals. Method: Operational optimization of the process was conducted using central composite design (CCD), considering the independent variables: dimensionless vibration number, supersaturation level, and seed population. The operating temperature was set at 55°C. The condition yielding maximum mass was utilized to study the growth kinetics over a time range from 0.5 hours to 2 hours. Characteristic dimension and concentration were monitored as a function of crystallization time. Results and Discussion: In two hours of operation, the crystal mass increased by 157%, and the characteristic dimension increased to approximately 42%. Growth rates, overall mass transfer coefficient, and growth kinetics order were determined. Originality: This article consists of a contribution to the use of vibration to improve crystallization with the application of vibration to improve the transfer of heat and mass.

Chemical route for synthesis of citric acid from orange and grape juices

Citrus fruits contain sufficient citric acid, which is the main tricarboxylic acid. The properties of citric acid make it an important additive in various process industries. This experimental study aims to produce citric acid from orange and grape juices. The chemical route for the synthesis of citric acid from citrus juices involves three steps: (i) neutralization to adjust pH (9-11) with a 2.8 M NaOH solution, (ii) addition of CaCl2 solution (40.3-41.1% w/v), and (iii) acidification with an H2SO4 solution (1.5-2.3 M) to produce citric acid. In this study, the fruits were peeled, crushed, filtered, neutralized, added CaCl2 solution, and acidified to obtain citric acid. The experiments were carried out by varying the final pH of the solution and the concentrations of CaCl2 and H2SO4 solutions, maintaining the total volume constant. A maximum citric acid yield of 91.1% and 79.8% were achieved from orange and grapefruits, respectively, at the optimum final pH of the solution and the concentrations of CaCl2 and H2SO4 solutions at 10, 40.7% w/v, and 1.9 M, respectively. Finally, the purified citric acid crystals were characterized using FTIR and XRD. Thus, it could be concluded that orange fruit would be a promising source for citric acid production than grape.

Multiobjective optimization and experimental validation for batch cooling crystallization of citric acid anhydrate

Multiobjective optimization (MOO) of crystallization systems is gaining importance due to its ability to handle multiple conflicting objectives together for finding optimal operating policies. The present study focuses on batch cooling crystallization of citric acid. Among the two forms of citric acid, citric acid anhydride (CAA) is chosen for experimentation as no such study is available. MOO is carried out to seek optimal cooling policy for unseeded cooling crystallization of CAA to maximize mean crystal size while minimizing variance in size. In this procedure, temperature is discretized using piecewise constant-control vector parameterization which is simple and convenient for practical implementation. The model reported in literature is suitably modified for solubility parameters which are verified experimentally, and employed for optimization. One of the optimal solutions from the Pareto solution set is implemented through experimentation successfully and the measured product crystal properties are comparable to the predicted results obtained through optimization.

Phosphate recovery through struvite-family crystals precipitated in the presence of citric acid: mineralogical phase and morphology evaluation

ABSTRACTPrecipitation strategy of struvite-family crystals is presented in this paper to recover phosphate and potassium from a synthetic wastewater in the presence of citric acid at elevated temperature. The crystal-forming solutions were prepared from crystals of MgCl2 and NH4H2PO4 with a molar ratio of 1:1:1 for Mg+2, , and , and the citric acid (C6H8O7) was prepared (1.00 and 20.00 ppm) from citric acid crystals. The Rietveld analysis of X-ray powder diffraction pattern confirmed a mixed product of struvite, struvite-(K), and newberyite crystallized at 30°C in the absence of citric acid. In the presence of citric acid at 30° and 40°C, an abundance of struvite and struvite-(K) were observed. A minute impurity of sylvite and potassium peroxide was unexpectedly found in certain precipitates. The crystal solids have irregular flake-shaped morphology, as shown by scanning electron microscopy micrograph. All parameters (citric acid, temperature, pH, Mg/P, and N/P) were deliberately arranged to control struvite-family crystals precipitation.

Acoustic emission during the solvent mediated cooling crystallization of citric acid

The potential of Acoustic Emission (AE) for controlling crystallization processes is investigated. The sensing technology is successfully applied to monitor the batch cooling crystallization of citric acid (CA) in water. The solvent-mediated phase transition between the anhydrous and the monohydrated forms of CA is clearly detected from the recorded acoustic measurements. A tremendous amount of acoustic data is recorded by the equipment, and the analysis of the data is focused on the evaluation of AE as a new sensor for monitoring the basic steps of the crystallization processes (i.e., nucleation, growth, phase transition, etc.) A time- and frequency-domain analysis is presented which shows the wealth of the technique. It is finally concluded that AE allows very early detection of nucleation events, provides a means of monitoring the development of the crystallization process and allows monitoring phase transition phenomena obtained through cooling. It is thus suggested that acoustic emission could be valuable in the development of new crystallization monitoring and control strategies: this is all the more interesting that the acoustic piezo-sensor is non-intrusive and does not require any sampling of the slurry, two features which are of tremendous importance in the field of cooling crystallization processes.

Role of Lipid Blooming and Crystallite Size in the Performance of Highly Soluble Drug-Loaded Microcapsules

Hot-melt coating is of growing interest, because it does not require solvents, resulting in reduced process times and costs. However, excipients for this technology are mainly triacylglycerides (TAGs) or their derivatives, which exhibit polymorphism, surface disruption, and complex crystallite networks, affecting the release profile of produced microcapsules. In this work, anhydrous citric acid crystals were coated with molten tristearin using conventional inlet air temperatures (microcapsules A) and temperatures above the melting point of α-form (microcapsules B). Additionally, microcapsules A were tempered to achieve polymorphic stability (microcapsules AB). The product yield and coating efficacy were above 90% and 97%, respectively, demonstrating the feasibility and efficacy of the process. Small angle X-ray scattering analysis confirmed that the tristearin shell of microcapsules B is in the β-form with a larger average crystallite size than microcapsules A and AB. Scanning electron microscopy images revealed a nonbloomed surface of microcapsules B. We showed that blooming does not play a critical role in the drug release, but the apparent diffusion coefficient of drug is dramatically reduced by increasing TAGs crystallite size and resulting tortuosity. This work brings new insights on the micrometric properties of solid lipid dosage forms, being an important step to prevent the overuse of excipients with unknown toxicity.

Acoustic Emission, a New Sensor for Monitoring Industrial Crystallization Processes

The potential of Acoustic Emission (AE) for monitoring industrial crystallization processes is investigated through the monitoring of two typical crystallization systems. The sensing technology is successfully applied to monitoring the batch cooling solution crystallization of Citric Acid (CA) in water, which exhibits a anhydrous to monohydrate phase transition. The technique is also applied to monitoring the precipitation of salicylic acid from its sodium salt. A huge amount of acoustic data is recorded by the AE system, and the analysis of this data set is focused on the evaluation of AE as a new sensor for monitoring the basic steps of the crystallization process (i.e., nucleation, growth, phase transition, etc.) A time- and frequency domain analysis is presented which shows the wealth of the technique. It is finally concluded that AE allows a very early detection of nucleation events, provides a means of monitoring the development of the crystallization or precipitation process and allows monitoring solvent-mediated phase transition phenomena occurring under cooling. It is thus suggested that acoustic emission could be valuable in the development of new crystallization monitoring and control strategies: this is all the more interesting that the acoustic piezo-sensor is non-intrusive and does not require any sampling of the slurry, two features which are of tremendous importance in the field of cooling crystallization processes.

Online analytical investigations on solvent‐, temperature‐ and water vapour‐induced phase transformations of citric acid

AbstractIt was demonstrated exemplarily for the crystallization of citric acid that the usage of an ultrasound device as well as Raman spectroscopy enables the inline measurement and the control of phase transitions. The influence of different solvent compositions (water and ethanol‐water) on the crystallization of citric acid was investigated. By increasing the ethanol content the transformation point was shifted towards higher temperatures. In addition, a strong impact on the nucleation point as well as on the crystal habit was detected in ethanol‐water mixtures. The results lead to the assumption that a citric acid solvate exists, which is, however, highly unstable upon isolation from mother liquor and converts fast into the known anhydrate or monohydrate forms of citric acid. The presence of such a solvate, however, could not be proven during this study. Furthermore, factors such as temperature and humidity which might influence the phase transition of the solid product were analyzed by Hotstage‐Raman Spectroscopy and Water Vapor Sorption Gravimetry‐Dispersive Raman Spectroscopy. Both, tempereature as well as humidity show a strong influence on the behaviour of CAM.

Citric acid crystallization process in dense phase using vibrated bed

This study evaluated mass yield, in crystallization of citric acid on a vibrated bed, using a large seed population (dense phase). A stainless steel crystallizer, jacketed and trunk-conical shaped was used in the crystallization experiments. The shaking system consisted of two perforated disks coupled to a mobile axle, which was connected to an eccentric. A central composite design (CCD) was used considering three independent variables: supersaturation level, dimensionless vibration number, and crystallization time, while the seed population (100,000U) and operation temperature (55°C) were fixed. Optimization of the experimental data obtained in the CCD was done finding the condition of maximum yield, 164.7%, which was experimentally tested and resulted in yield of 187.7%. An experimental simulation of serial crystallizers was studied, obtaining 166.9% yield, which was effective for obtaining crystals of greater final dimension.

A method of characteristics for solving population balance equations (PBE) describing the adsorption of impurities during crystallization processes

Possible hindering effects of impurities on the crystal growth were shown to take place because of the adsorption of impurity species on the crystal surface. Transient features of this adsorption were observed, such that the growth of a given crystal does not depend on supersaturation only, but also on the time a given particle spent in contact with impurities present in the mother liquor. Meanwhile, few kinetic models describe the effect of impurities on the growth of crystals in solution, and published models are usually derived from data obtained, thanks to specific experiments based on the evaluation of the growth rate of single crystals. Such models are obviously questionable because, in the industrial practice, distributed properties of crystals are actually involved. Considering the “time of contamination” of particles as a new internal variable is thus made necessary. This is the reason why a specific PBE resolution algorithm is presented in this paper. The numerical scheme for the resolution of PBEs is based on the method of characteristics and shown to allow fast and accurate simulation of transient features of the crystal size distribution in the particular case when the growth or nucleation rates are assumed to exhibit unsteady-state dynamics. The algorithm is finally used to simulate the isothermal desupersaturation crystallization of citric acid in water.

Citric acid as a pH-modifying additive in an extended release pellet formulation containing a weakly basic drug

Background: An extended release pellet formulation (ACES®) of the weakly basic drug propiverine was developed with spheronized citric acid crystals as starter cores. Method: Coated pellets, consisting of several layers of functional coatings, were manufactured by fluid bed coating. Different coating levels were examined with regard to their effect on drug release. Release profiles from the formulations with or without pH modifier and the free base as well as the hydrochloride salt of the active ingredient were compared. Results: The coated citric acid starter cores led to a controlled release of the drug and the pH modifier, resulting from modulation of the microenvironmental pH throughout the dissolution period of 17 hours. If microcrystalline cellulose pellets are used as starter cores drug release is strongly pH-dependent. Significant differences in the drug release profiles were observed between the formulations containing the free drug base and those with the hydrochloride salt as a result of an altered microenvironmental pH. Conclusion: The presented extended release pellet formulation is able to maintain a low pH within the pellet core and thus a sufficiently high drug solubility. By maintaining a low pH inside the pellets, a controlled drug release can be achieved.

Crystallization of Monohydrate Citric Acid. 2. Modeling through Population Balance Equations

Experimental data about both the liquid and the solid phases during seeded batch crystallizations of citric acid (CA) in water were obtained using in situ Raman spectroscopy and image acquisition. These experimental results were reported in a previous paper in this issue (Caillet, A., et al. Cryst. Growth Des. 2007, 7, 2080−2087). The present paper is now focused on the mathematical modeling of the desupersaturation process during the crystallization of monohydrate citric acid (MCA), which is the stable form at 15 °C. Both the crystallization of MCA (monohydrate) and the dissolution of the anhydrous (ACA) form were investigated. The model is based upon population balance equations (PBEs) describing the evolution of the crystal size distribution (CSD) during batch seeded operations. The estimation of the kinetic parameters of MCA nucleation and growth, and of the dissolution of ACA, was performed using nonlinear optimization techniques. For various operating conditions (modifications of the initial supersaturation and of the seed amount), the two PBE models represent satisfactorily the experimental behavior of the process. In particular, activated secondary nucleation is shown to explain particular features of the solute/solvent system that were observed previously.

Importance of Heterogeneous Energy Dissipation in the Modeling and Optimization of Batch Cooling Crystallization

The influence of the local energy dissipation rate on the kinetics of crystallization has been widely reported in the literature. It is also well-known that, in an agitated vessel, the energy dissipation rate (EDR) usually exhibits a heterogeneous distribution. The objective of this paper is to investigate the validity of a homogeneity assumption associated with the EDR for batch cooling crystallization through numerical simulations and optimization studies. The results of the numerical studies, based on a homogeneous model, are compared with those obtained from a compartmental model that takes into account the distribution of the EDR within a vessel. The crystallization of citric acid in water is the system that forms the basis of the comparative study. The results of the numerical simulation studies for the crystallizer, in the presence of sufficient macro-mixing, confirm that the assumption of homogeneity, with respect to the EDR, is valid only when a linear relationship exists between the secondary nucleation rate and the local EDR. When the relationship is of an order lower (higher) than unity, the average product size predicted by a compartmental model tends to be higher (lower) than that predicted by a model where homogeneity is assumed. Such observations are confirmed through a theoretical analysis. The numerical studies further revealed that the difference between the computational and homogeneous model can be considerable when the order significantly exceeds unity. This becomes more pronounced when the secondary nucleation rate increases. However, in contrast, through the optimization of the temperature profile to maximize the average product size, qualitatively similar cooling profiles are attained. This is not dependent on whether the compartmental or homogeneous model is utilized.

Role of Deliquescence Lowering in Enhancing Chemical Reactivity in Physical Mixtures

Mixtures of deliquescent solids are susceptible to deliquescence lowering, where water vapor condensation occurs in mixtures at a lower critical relative humidity (RH(0mix)) than individual component critical relative humidities (RH(0)s). The purpose of this study was to evaluate the effect of deliquescence lowering on chemical reactivity. Sucrose, citric acid and their physical mixtures were characterized using vapor sorption analysis to determine RH(0) and RH(0mix). Acid-catalyzed sucrose hydrolysis kinetics was determined using polarimetric analysis. Physical mixtures of sucrose and citric acid crystals were prepared and stored at various relative humidities at 22 degrees C. For these physical mixtures, sucrose hydrolysis was found to occur only when the environmental RH exceeded RH(0mix). Degradation kinetics correlated with the storage RH, being fastest at higher RH. In addition, a lag period was initially observed, which was most prominent for samples stored close to RH(0mix). With exposure to RHs below RH(0mix), no sucrose degradation was detected over the experimental time period. In conclusion, mixtures of deliquescent solids showed increased water sorption at lower RHs, which caused solid dissolution and subsequently led to an increase in the chemical reactivity.

Nucleation, Growth, and Pseudo-Polymorphic Behavior of Citric Acid As Monitored in Situ by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy

The crystallization, dissolution, and associated pseudo-polymorphic behavior of citric acid crystals from aqueous solution is investigated using temperature-programmed and isothermal batch experiments. Quantitative attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy is used to measure in situ the solution concentration and hence the reactant supersaturation over a wide range of solution undercoolings within the metastable zone. Detailed mapping out of the solubility−supersolubility diagram reveals poor nucleation behavior as characterized by a very wide metastable zone width (typical value, 55 °C for a cooling rate of 0.05 K/min). Simultaneous ATR FTIR and optical turbidometric measurements are used to cross-correlate the supersaturation driving force to the nucleation behavior as followed prior to and during crystallization within the metastable zone. Both temperature-programmed and isothermal measurements reveal behavior consistent with spontaneous liquid-phase separation wi...

Identification and Prevention of Insoluble Reaction Products Forming after Dissolution of Effervescent Multi-Vitamin Tablets

AbstractTwo problems of an unacceptable nature were experienced during the formulation of effervescent multi-vitamin and mineral tablets. When tablets containing ascorbic acid, calcium carbonate and vitamins, combined with ordinary effervescent excipients and sodium benzoate as lubricant, were dissolved, fine needles formed during effervescence. These needles float on top of the solution, making the product unattractive. During effervescence of a second tablet containing magnesium oxide and calcium carbonate, combined with ascorbic acid, a flake-like sediment formed. Infrared spectrophotometry, differential scanning calorimetry and atomic absorption analysis showed that the needles were benzoic acid, while the flakes were citrates - mainly calcium citrate. These problems were overcome by substituting the benzoic acid with micronised polyethylene glycol 6000 and by not including citric acid during the granulation stage but to add coarse citric acid crystals to the dry granules - composed of the rest of the...

Increased salivary cortisol in severe dental anxiety.

The aim of the present study was to investigate the feasibility of saliva collection from highly anxious dental patients and to evaluate whether salivary cortisol concentrations could discriminate between 13 highly anxious dental patients and 13 non-anxious subjects. Whole mixed saliva was sampled by suction after stimulation with citric acid crystals. Salivary free cortisol levels were measured in duplicate by radioimmunoassay. Collection of saliva took 2-5 min and was not experienced as unpleasant. Salivary free cortisol concentrations were significantly elevated if the patients manifested anxiety according to the scores on the Dental Anxiety Scale. The measurement of salivary cortisol may be a convenient method for the assessment of dental anxiety.

The effect of anticoagulants, enzyme inhibitors and long term storage on the extraction of known concentrations of methionine enkephalin in human plasma

The stability of methionine enkephalin (M-E) during long term storage was investigated using various anticoagulants and enzyme inhibitors, eg EDTA, heparin, trasylol, citric acid. Plasma was stored for different lengths of time up to six weeks. High pressure liquid chromatography (HPLC) was used to separate and quantify M-E. We found that EDTA, heparin or trasylol per se are ineffective in preserving M-E for short term extraction. Blood collected in chilled heparin tubes with citric acid crystals and the plasma further acidified with hydrochloric acid gave the highest recovery. With storage times up to six weeks further degradation was marked in samples taken in plain tubes but did not occur with tubes containing citric acid crystals and hydrochloric acid. Enkephalins normally occur in biological tissues and fluids in very low concentration pmo1/g or m1 1,2. The source of M-E in blood is so far unknown. There are speculations that it could be from the adrenal medulla, 3,4 and the ovary 5. Enkephalins are known to influence a variety of physiological processes. Among these are their effects on pain, respiration, blood pressure, behaviour, temperature, food intake 6,7 and the secretiion of several pituitary hormones 8,9,10. They may act as neurotransmitters of neuromodulators 11. It is well known that the physiological activity of enkephalins is transitory with a half life in vitro of two minutes due to their rapid degradation by proteolytic enzymes. Consequently the quantitative analysis of enkephalins is inaccurate unless effective methods to inhibit these enzymes are employed. To minimise the effect of inter-assay variation, analysis is preferably of large batches and long-term storage of specimens is required. The purpose of this study is to compare the effect of long term storage following the use of various agents to inhibit enzyme activity.

Monitoring Theophylline Therapy Using Citric Acid-Stimulated Saliva in Infants and Children With Asthma

Saliva stimulation is required for measurement of drugs in saliva. Chewing on a piece of paraffin, which is the method usually used for saliva stimulation, requires cooperation of the patient and, thus, is inapplicable in infants and young children. To assess the value of determining theophylline concentrations from noninvasively obtained saliva in this age group, we studied the theophylline plasma to saliva concentration ratio in citric acid-stimulated saliva. Theophylline concentration was measured in 137 simultaneously obtained paired specimens of plasma and saliva from 68 patients 2 1/2 months to 14 years of age treated with theophylline for asthma (dosage 20.8 +/- 5.2 mg/kg/d, mean +/- SD). Saliva secretion was stimulated by placing citric acid crystals on the tongue. A strong and highly significant correlation was observed between both determinations (r = .96; P less than .01). The plasma to saliva ratio was 1.78 +/- 0.22 (mean +/- SD), with theophylline concentrations between 3.1 and 32.1 micrograms/mL of plasma. The ratio of estimated to actual plasma theophylline concentrations was 1.02 +/- 0.12 (mean +/- SD). Interindividual coefficient of variation of plasma to saliva theophylline concentrations ratios was 12.4%; mean intraindividual coefficient of variation was 5.3%. The use of citric acid for saliva stimulation is easily applicable to infants and young children. Compared with blood drawing, stimulation of saliva secretion by citric acid is painless and noninvasive, is more readily accepted to patients, is at least as clinically relevant for theophylline determination, and allows frequent measurements of drug levels for individualization of the dosage with samples taken at home.(ABSTRACT TRUNCATED AT 250 WORDS)

83 RELIABLE NON-INVASIVE MONITORING OF THEOPHYLLTNE THERAPY IN INFANTS AND CHILDREN: MEASUREMENT OF SALIVA THEOPHYLLINE CONCENTRATIONS

The use of saliva (Sa) theophylline (Th) for monitoring Th therapy is not routinely used in infants and young children due to the inapplicability of the usual technique (chewing on a piece of paraffin) to obtain stimulated Sa in this age group. Simultaneous blood and Sa samples mere obtained in 57 infants and children (age: 3 mo-14 ys; mean: 3.3ys) under Th therapy. Th was given po (slow release preparations or elixir) or i.v. Mean ± SD dose was 21.3±6.4 mg/kg/day. Sa secretion was stimulated by placing citric acid crystals on the tongue. Plasma (P1) and Sa Th mas analysed by competitive fluorescence polarization immunoassay (TDx). Mean ± SD P1/Sa Th concentration ratio was 1.78±0.25 within a wide PI Th concentration range (3.1-32.1 meg/ml). Good correlation existed between both determinations (r=0,98). Interindividual coefficient of variation (CV) was 14%; mean intraindiuidual CV was 5.2%. Mean estimated/actual Pl Th ratios determined in the following 48 samples studied was 0.98±0.11, CV 11.2%. Th measurements in citric-acid stimulated saliva represent a convenient, non-invasive and reliable method for monitoring theophylline therapy in infants and children.