Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule "Soft" Constraints.

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Markovic et al., 2019), was applied. An improved and more detailed experimental design of the Nor solubility measurement allowed us to exploit the full capacity of the pH-RSF method. Complex equilibria in the aqueous phase (cationic and anionic complex formation between Nor and the phosphate) and solid-phase transformations (Nor free base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts) were characterized by a detailed analysis of the solubility measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth, on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the formulation of drug products.

Disproportionation of Pharmaceutical Salts: pHmax and Phase-Solubility/pH Variance.

A multiphasic mass action equilibrium model is used to show that the critical pH in the acid-base disproportionation of a solid salt into its corresponding solid free-base form in aqueous suspensions, widely known as "pHmax", is incompletely interpreted. It is shown that the traditional thermodynamic model does not predict the invariance of pH and solubility during the salt-to-free-base conversion process in an alkalimetric titration. Rather, the conversion entails a range of pH and solubility values, depending on the amount of added excess salt above that needed to form a saturated solution. A more precise definition is proposed for pHmax (pH at the maximum solubility of a eutectic mixture), and three new terms are introduced: pHmin (pH at the minimum solubility of the eutectic mixture), pHδ (disproportionation invariant pH within the eutectic, i.e., the equilibrium pH of a spontaneously disproportionating salt slurry), and pHγ (Gibbs pH at which disproportionation yields equimolar amounts of excess salt and excess free-base solids within the eutectic). Two test compounds with reported multiple salts and the free-base solubility values were selected to illustrate the expanded concepts, the bases WR-122455 and RPR-127963. Also, dibasic calcium phosphate was selected as an ionizable test excipient. The salts are designated in the study as µ-type, when they are thermodynamically stable with respect to spontaneous disproportionation in pure water (e.g., WR-122455 salts), and δ-type, when they are predicted to spontaneously disproportionate in pure water (e.g., RPR-127963 salts). In an alkalimetric titration, when an acidified suspension of a salt of a basic molecule is titrated with a strong base (e.g., NaOH), the passage across the eutectic domain (bounded by pHmax and pHmin) is often characterized by (a) minimum in ionic strength either at pHmax (µ-type salt) or pHδ (δ-type salt) and (b) maximum buffer capacity at pHγ. When the alkalimetric titration is performed with a large excess of added salt, a wide eutectic domain forms: pHmax and pHδ remain invariant, but pHmin and pHγ shift substantially in pH. The acid-base mass action model described here can be useful in predicting the stability of salt formulations in mixtures with excipients that can act as pH modifiers.

Ultrasensitive photoelectrochemical platform with micro-emulsion-based p-type hollow silver iodide enabled by low solubility product (Ksp) for H2S sensing.

Since visible-light (VL) accounting for massive solar radiation energy, a large amount of attention has been paid to the development of highly efficient visible-light-driven (VLD) semiconductor materials. However, despite recent efforts to construct VL active material, hollow structure-based silver iodide (AgI) with appropriate band gap and a large surface area are limited because of lack of a proper synthesis method. Herein, hollow AgI with p-type semiconductor behavior is constructed on the basis of micro-emulsion strategy, which enables admirable cathode photoelectrochemical (PEC) response. The as-prepared hollow AgI is applied to fabricate the PEC sensing platform and reveals a low limit of detection of 0.04 fM and a wide dynamic range up to 5 orders of magnitude toward H2S. The PEC sensing mechanism is supposed to the 'signal-off' pattern on account of the ultralow solubility product (Ksp) of Ag2S, derived from the precipitation reaction due to the high affinity between sulfide ion and Ag+. Besides, the hollow structure of AgI provides sufficient surface area forin situproducing Ag2S that serves as recombination center of carrier, thus causing the efficient quenching of photocurrent signals. This work broadens the horizon of structuring VLD semiconductor nanomaterials andKsp-based H2S sensing.

Cocrystal Solubility Product Prediction Using an in combo Model and Simulations to Improve Design of Experiments.

PURPOSE: To predict the aqueous solubility product (K sp ) and the solubility enhancement of cocrystals (CCs), using an approach based on measured drug and coformer intrinsic solubility (S 0API , S 0cof ), combined with in silico H-bond descriptors. METHOD: A regression model was constructed, assuming that the concentration of the uncharged drug (API) can be nearly equated to drug intrinsic solubility (S 0API ) and that the concentration of the uncharged coformer can be estimated from a linear combination of the log of the coformer intrinsic solubility, S 0cof , plus in silico H-bond descriptors (Abraham acidities, α, and basicities, ß). RESULTS: The optimal model found for n:1 CCs (-log10 form) is pK sp = 1.12 n pS 0API + 1.07 pS 0cof + 1.01 + 0.74 αAPI·ßcof - 0.61 ßAPI; r 2 = 0.95, SD = 0.62, N = 38. In illustrative CC systems with unknown K sp , predicted K sp was used in simulation of speciation-pH profiles. The extent and pH dependence of solubility enhancement due to CC formation were examined. Suggestions to improve assay design were made. CONCLUSION: The predicted CC K sp can be used to simulate pH-dependent solution characteristics of saturated systems containing CCs, with the aim of ranking the selection of coformers, and of optimizing the design of experiments.

Characterization, dissolution and solubility of synthetic cadmium hydroxylapatite [Cd5(PO4)3OH] at 25-45°C.

BACKGROUND: The substitution of Ca(2+) in Ca-hydroxylapatite by toxic Cd(2+) can cause the forming of Cd-hydroxylapatite and is a significant issue in a great variety of research areas, which hence needs an understanding of the essential physicochemical characteristics. Unfortunately, the solubility product and thermodynamic data for Cd-hydroxylapatite in water under a variety of conditions now are lacking. Little information has been reported by previous researchers. Additionally, the dissolution mechanism of Cd-hydroxylapatite has never been studied. RESULTS: Dissolution of the synthetic cadmium hydroxylapatite [Cd-HAP, Cd5(PO4)3OH] in HNO3 solution (pH = 2), ultrapure water (pH = 5.6) and NaOH solution (pH = 9) was experimentally studied at 25, 35 and 45°C. Characterization by XRD, FT-IR and FE-SEM proved that Cd-HAP solids showed no recognizable change during dissolution. For the Cd-HAP dissolution in aqueous acidic media at initial pH 2 and 25°C, the solution cadmium and phosphate concentrations increased rapidly and reached the peak values after 20-30 days and 10 days reaction, respectively. Thereafter, the Cd-HAP dissolution rate decreased slowly, whereas the solution Cd/P molar ratio increased constantly from 1.65-1.69 to 6.61-6.76. The mean K sp values for Cd5(PO4)3OH were determined to be 10(-64.62) (10(-64.53)-10(-64.71)) at 25°C, 10(-65.58) (10(-65.31)-10(-65.80)) at 35°C and 10(-66.57) (10(-66.24)-10(-66.90)) at 45°C. Based on the obtained solubility data from the dissolution at initial pH 2 and 25°C, the Gibbs free energy of Cd5(PO4)3OH forming [Formula: see text] was determined to be -3,970.47 kJ/mol (-3,969.92 to -3,970.96 kJ/mol). Thermodynamic parameters, ΔG (0), ΔH (0), ΔS (0), and [Formula: see text] for the dissolution process of Cd-HAP in aqueous acidic media at initial pH 2 and 25°C were calculated 368,710.12 J/K mol, -158,809.54 J/mol, -1,770.20 and -869.53 J/K mol, respectively. CONCLUSIONS: Based on the experimental results of the present work and some previous researches, the cadmium hydroxylapatite (Cd-HAP) dissolution in aqueous media is considered to have the following coincident processes: the stoichiometric dissolution coupled with protonation and complexation reactions, the non-stoichiometric dissolution with Cd(2+) release and PO4 (3-) sorption and the sorption of Cd(2+) and PO4 (3-) species from solution backwards onto Cd-HAP surface. The obtained solubility products (K sp) 10(-64.62) (10(-64.53)-10(-64.71)) for Cd-HAP was approximately 7.62-5.62 log units lower than 10(-57)-10(-59) for calcium hydroxylapatite (Ca-HAP).Graphical abstractDissolution of cadmium hydroxylapatite [Cd5(PO4)3OH].

Dissolution behaviors of a visible-light-responsive photocatalyst BiVO4: Measurements and chemical equilibrium modeling.

Despite of the extensive research in semiconductor photocatalysis with respect to material and device innovations, much of the fundamental aquatic chemistry of those new materials that governs their environmental hazard and implications remains poorly understood. BiVO4 has long been recognized as a promising visible-light-responsive photocatalyst. However, the solubility product (Ksp) of BiVO4 and the mechanistic understanding of the non-stoichiometric dissolution of BiVO4 remain unclear. Here, we investigated the solubility of BiVO4 via the observation on its non-stoichiometric dissolution in the pH range of 4-9. Combining dissolution experiments, adsorption behavior and thermodynamic equilibrium calculations, the Ksp of BiVO4 was determined to be 10-35.81±0.51. The solubility and stability of BiVO4 were strongly pH-dependent, with the lowest solubility and highest stability near pH 5. Furthermore, we tested the effect of illumination on the dissolution of BiVO4, which was significantly enhanced by light. Under both dark and illumination conditions, adsorption of dissolved bismuth by BiVO4 solids was the main reason for the non-stoichiometric dissolution of BiVO4, and could be modeled by including an additional surface complexation reaction. Thus, the results highlighted the importance of considering the dissolution of photocatalysts, and presented a feasible method to evaluate environmental stability and risks of other semiconductor materials.

How the Addition of Chitosan Affects the Transport and Rheological Properties of Agarose Hydrogels.

Agarose hydrogels enriched by chitosan were studied from a point of view diffusion and the immobilization of metal ions. Copper was used as a model metal with a high affinity to chitosan. The influence of interactions between copper and chitosan on transport properties was investigated. Effective diffusion coefficients were determined and compared with values obtained from pure agarose hydrogel. Their values increased with the amount of chitosan added to agarose hydrogel and the lowest addition caused the decrease in diffusivity in comparison with hydrogel without chitosan. Liesegang patterns were observed in the hydrogels with higher contents of chitosan. The patterns were more distinct if the chitosan content increased. The formation of Liesegang patterns caused a local decrease in the concentration of copper ions and concentration profiles were affected by this phenomenon. Thus, the values of effective diffusion coefficient covered the influences of pore structure of hydrogels and the interactions between chitosan and metal ions, including precipitation on observed Liesegang rings. From the point of view of rheology, the addition of chitosan resulted in changes in storage and loss moduli, which can show on a "more liquid" character of enriched hydrogels. It can contribute to the increase in the effective diffusion coefficients for hydrogels with higher content of chitosan.

Salt Solubility and Disproportionation - Uses and Limitations of Equations for pHmax and the In-silico Prediction of pHmax.

A multiphasic mass action equilibrium model was used to study the phase properties near the critical pH ('pHmax') in an acid-base transformation of a solid drug salt into its corresponding solid free base form in pure water slurries. The goal of this study was to better define the characteristics of disproportionation of pharmaceutical salts, objectively (i) to classify salts as µ-type (microclimate stable) or δ-type (disproportionation prone) based on the relationship between the calculated pHmax and the calculated pH of the saturated salt solution, (ii) to compare the distribution of µ/δ-type salts to predictions from the disproportionation potential equation introduced by Merritt et al.,20 (iii) to determine if the intrinsic solubility of the free base, S0, can be predicted from the measured µ-type salt solubility as a means of estimating the value of pHmax, (iv) to determine S0 directly from the measured δ-type salt solubility, and (v) to address some of the limitations of the equations commonly used to calculate pHmax. When the salt solubility is measured for a basic API (pKa of which is known), but the experimental value of S0 is unavailable, a potentially useful simple screen for disproportionation is still possible, since pHmax can be estimated from a 'µ-predicted' (objective iii) or 'δ-measured' S0 (objective iv). Twelve model weak base API were selected in the study. For each API, 2-17 different salt forms with reported salt solubilities in distilled water were sourced from the literature. In all, 73 salt solubility values based on 29 different salt-forming acids comprise the studied set. All the corresponding free base solubility values were available. The pKa values for all the acids and bases studied are generally well known. For each API salt, an acid-base titration simulation was performed, anchored to the measured salt solubility value, using the general mass action analysis program pDISOL-X. The log S-pH profiles were drawn out by analytic continuity from pH 0 to 13, as described in detail previously.24 Potentially useful in-silico models were developed that correlate pS0 to linear functions of the salt solubility in water, pSw, the partition coefficient of the salt-forming acid (log POCTacid) and the melting point (mp) of the drug salt, thereby enabling the derivation of the approximate pHmax value from the predicted pS0.

Self-Assembly of a 3D Hollow BiOBr@Bi-MOF Heterostructure with Enhanced Photocatalytic Degradation of Dyes.

Considering the flexibility, adjustable pore structure, and abundant active sites of metal-organic frameworks (MOFs), rational design and fine control of the MOF-based hetero-nanocrystals is a highly important and challenging subject. In this work, self-assembly of a 3D hollow BiOBr@Bi-MOF microsphere was fabricated through precisely controlled dissociation kinetics of the self-sacrificial template (BiOBr) for the first time, where the residual quantity of BiOBr and the formation of Bi-MOF were carefully regulated by changing the reaction time and the capability of coordination. Meanwhile, the hollow microstructure was formed in BiOBr@Bi-MOF through the Oswald ripening mechanism to separate photogenerated electron-hole pairs and increase the adsorption capacity of Bi-MOF for dyes, which significantly enhanced the photocatalytic degradation efficiency of RhB from 56.4% for BiOBr to 99.4% for the optimal BiOBr@Bi-MOF microsphere. This research broadens the selectivity of semiconductor/MOF hetero-nanocrystals with reasonable design and flexible synthesis.

The removal of heavy metal cations by sulfidated nanoscale zero-valent iron (S-nZVI): The reaction mechanisms and the role of sulfur.

In this study, the reaction between sulfidated nanoscale zero-valent iron (S-nZVI) and heavy metal cations as well as the role of sulfur were investigated. The results showed the corrosion products of S-nZVI were lepidocrocite (γ-FeOOH) or/and magnetite (Fe3O4), depending on heavy metal species. While the removal of Hg(II), Ag(I), Cu(II), and Pb(II) by S-nZVI was rapid and could achieve over 99% within 5 mins, the removal of Ni(II) and Zn(II) was low in efficiency and unstable. Sulfur was existed as iron sulfides at fresh S-nZVI, but was displaced by the heavy metals and formed the related sulfide compound, or oxidized to S0 and SO42-. The removal mechanisms are strongly dependent on the solubility product constant (Ksp) of metal sulfides. For Hg(II) and Ag(I), with Ksp of corresponding metal sulfides much lower than that of iron sulfide, the removal mechanism is the displacement reaction. For Cu(II) and Pb(II), with Ksp of corresponding metal sulfides moderately lower than that of iron sulfide, the removal mechanisms are the displacement reaction and complexation with surface groups of S-nZVI. For Zn(II) and Ni(II), whose Ksp of corresponding metal sulfides slightly lower than that of iron sulfide, are mainly removed by complexation with surface groups of S-nZVI.

Accountancy for intrinsic colloids on thorium solubility: The fractionation of soluble species and the characterization of solubility limiting phase.

The extensive hydrolysis of tetravalent actinides leads to polynuclear formations through oxygen bridging facilitating the formation of colloids as end products. The pH, ionic strength has phenomenal effects on Thorium colloids formation. The quantitative estimation of colloids facilitates the fraction of soluble fraction into ionic, polymeric and colloidal forms of thorium. The colloids accountability and precipitate characterization explains the discrepancies in estimated solubility limits. The supernatants of long equilibrated (∼3 years) saturated thorium solution under various pH (5- 11) and ionic strengths (0-3 M NaClO4) were analysed by Inductively Coupled Plasma Mass Spectrometer (ICP-MS) and Ion Chromatography (IC) to determine total and ionic thorium respectively. Laser Induced Breakdown Detection (LIBD) was employed to determine the colloid size and concentrations. The precipitates were characterized by calorimetry and XRD to determine the solubility limiting phase. The results of pH, IC, ICP-MS, and LIBD measurements on the aged thorium samples are discussed with regard to the mechanism of the formation of thorium colloids. The results revealed the formation of colloids having particle size (10-40 nm) at concentrations (109-1011 particles/mL). The colloids accountancy resulted in estimated solubility products to 2-4 orders lower than their inclusion as soluble thorium. The soluble thorium was fractionated quantitatively into ionic, polymeric and colloidal forms of thorium. The precipitates formed are found to be semi amorphous.

The solubility product extends the buffering concept to heterotypic biomolecular condensates.

Biomolecular condensates are formed by liquid-liquid phase separation (LLPS) of multivalent molecules. LLPS from a single ("homotypic") constituent is governed by buffering: above a threshold, free monomer concentration is clamped, with all added molecules entering the condensed phase. However, both experiment and theory demonstrate that buffering fails for the concentration dependence of multicomponent ("heterotypic") LLPS. Using network-free stochastic modeling, we demonstrate that LLPS can be described by the solubility product constant (Ksp): the product of free monomer concentrations, accounting for the ideal stoichiometries governed by the valencies, displays a threshold above which additional monomers are funneled into large clusters; this reduces to simple buffering for homotypic systems. The Ksp regulates the composition of the dilute phase for a wide range of valencies and stoichiometries. The role of Ksp is further supported by coarse-grained spatial particle simulations. Thus, the solubility product offers a general formulation for the concentration dependence of LLPS.

How Fluoride Protects Dental Enamel from Demineralization.

INTRODUCTION: How fluoride (F-) protects dental enamel from caries is here conveyed to dental health-care providers by making simplifying approximations that accurately convey the essential principles, without obscuring them in a myriad of qualifications. MATERIALS AND METHODS: We approximate that dental enamel is composed of calcium hydroxyapatite (HAP), a sparingly soluble ionic solid with the chemical formula Ca10(PO4)6(OH)2. RESULTS: The electrostatic forces binding ionic solids together are described by Coulomb's law, which shows that attractions between opposite charges increase greatly as their separation decreases. Relatively large phosphate ions (PO4 3-) dominate the structure of HAP, which approximates a hexagonal close-packed structure. The smaller Ca2+ and OH- ions fit into the small spaces (interstices) between phosphates, slightly expanding the close-packed structure. F- ions are smaller than OH- ions, so substituting F- for OH- allows packing the same number of ions into a smaller volume, increasing their forces of attraction. Dental decay results from tipping the solubility equilibrium Ca10(PO4)6(OH)2 (s) ⇔ 10Ca2+ (aq) + 6PO4 2- (aq) + 2OH- (aq) toward dissolution. HAP dissolves when the product of its ion concentrations, [Ca2+]10×[PO4 3-]6×[OH-]2, falls below the solubility product constant (Ksp) for HAP. CONCLUSION: Because of its more compact crystal structure, the Ksp for fluorapatite (FAP) is lower than the Ksp for HAP, so its ion product, [Ca2+]10×[PO4 3-]6×[F-]2, must fall further before demineralization can occur. Lowering the pH of the fluid surrounding enamel greatly reduces [PO4 3-] (lowering the ion products of HAP and FAP equally), but [OH-] falls much more rapidly than [F-], so FAP better resists acid attack.

Solubility-pH profile of desipramine hydrochloride in saline phosphate buffer: Enhanced solubility due to drug-buffer aggregates.

Although solubility-pH data for desipramine hydrochloride (DsHCl) have been reported previously, the aim of the present study was to critically examine the aqueous solubility-pH behavior of DsHCl in buffer-free and buffered solutions, in the presence of physiologically-relevant chloride concentration, using experimental practices recommended in the recently-published "white paper" (Avdeef et al., 2016). The computer program pDISOL-X was used to design the structured experiments (pH-RSF method), to process the data, and to refine the equilibrium constants. Low-to-high and high-to-low pH assays (using HCl, H3PO4, or NaOH to adjust pH) were performed on phosphate-buffered (0.12­0.15 M) saturated solutions of DsHCl in the pH 1.3-11.6 range. After equilibration (stirring 6 h, followed by 18 h stir-free sedimentation), filtration or centrifugation was used for phase separation. Concentration was measured using HPLC with UV/VIS detection. The 2:1 drug-phosphate solubility product (Ksp2:1 = [DsH+]2[HPO42-]) was determined from data in the pH 4-9 region. The free base of desipramine was prepared and used to determine the Ksp1:1 ([DsH+][H2PO4-]) in chloride-free acidified suspension. In addition, phosphate-free titrations were conducted to determine the intrinsic solubility, S0, and the 1:1 drug-chloride solubility product, KspDsHCl = [DsH+][Cl-]. Under the assay conditions, only the phosphate-free solutions showed some supersaturation near pHmax 8.0. In phosphate-containing solutions, pHmax was indicated at higher pH (8.8-9.6). Oils mixed with solids were observed to form in alkaline solutions (pH > 11). Notably, soluble drug-phosphate complexes appeared to form below pH 3.9 and above pHmax in saturated phosphate­containing saline solutions. This was indicated by the systematic pH shift to higher values in the log S-pH curve in alkaline solution than expected from the Henderson-Hasselbalch equation. For pH < 3.9, saturated phosphate-containing saline solutions exhibited elevated solubility, with drug-hydrochloride as the sole precipitate. Salt solubility products, intrinsic solubility, and complexation constants, which rationalized the data, were determined. Elemental, thermogravimetric (TGA), differential scanning calorimetric (DSC), and powder X-ray diffraction (PXRD) analyses were used to characterize the precipitates isolated from suspensions at different pH.

The effects of pH, surfactant, ion concentration, coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals.

Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin (MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate (IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Furthermore, single crystal structures of MYR, myricetin-isonicotinamide (MYR-INM) and myricetin-caffeine (MYR-CAF) cocrystals were analyzed to discuss the possible reasons for the enhancement of cocrystal solubility from the perspective of the spatial structure. The results indicated that the kinetic solubility of MYR cocrystals was modulated by pH and cocrystal coformer (CCF) ionization in buffer solution, while it primarily depended on the CCF solubility in pure water. In addition, the solubility of MYR cocrystals was increased in a concentration dependent fashion by the surfactant or ion concentration. The thermodynamic solubility of MYR-INM (1:3) cocrystals decreased with the increases of the pH value of the dissolution media. The IDR of MYR cocrystals was faster than that of MYR in the same medium and extremely fast in pH 4.5 buffer. The improved solubility of MYR cocrystals was probably related to the alternate arrangements of MYR and INM/CAF molecules and increased intermolecular distance. The present study provides some references to investigate the solubility behavior of pharmaceutical cocrystals.

Cocrystal solubility product analysis - Dual concentration-pH mass action model not dependent on explicit solubility equations.

A novel general computational approach is described to address many aspects of cocrystal (CC) solubility product (Ksp) determination of drug substances. The CC analysis program, pDISOL-X, was developed and validated with published model systems of various acid-base combinations of active pharmaceutical ingredients (APIs) and coformers: (i) carbamazepine cocrystal systems with 4-aminobenzoic acid, cinnamic acid, saccharin, and salicylic acid, (ii) for indomethacin with saccharin, (iii) for nevirapine with maleic acid, saccharin, and salicylic acid, and (iv) for gabapentin with 3-hydroxybenzoic acid. In all systems but gabapentin, the coformer is much more soluble than the API. The model systems selected are those with available published dual concentration-pH data, one set for the API and one set for the coformer, generally measured at eutectic points (thermodynamically-stable three phases: solution, cocrystal, and crystalline API or coformer). The carbamazepine-cinnamic acid CC showed a substantial elevation in the API equilibrium concentration above pH5, consistent with the formation of a complex between carbamazepine and cinnamate anion. The analysis of the gabapentin:3-hydroxybenzoic acid 1:1 CC system indicated four zones of solid suspensions: coformer (pH<3.25), coformer and cocrystal eutectic (pH3.25-4.44), cocrystal (pH4.44-5.62), and API (pH>5.62). The general approach allows for testing of many possible equilibrium models, including those comprising drug-coformer complexation. The program calculates the ionic strength at each pH. From this, the equilibrium constants are adjusted for activity effects, based on the Stokes-Robinson hydration theory. The complete speciation analysis of the CC systems may provide useful insights into pH-sensitive dissolution effects that could potentially influence bioavailability.

A Novel Kinetic Method to Measure Apparent Solubility Product of Bulk Human Enamel.

Introduction: Tooth enamel mineral loss is influenced by its solubility product value, which is fundamental to the understanding of de- and remineralization resulting from a carious or erosive challenge. Published pKsp values for human enamel and hydroxyapatite range from 110 to 126 suggesting a heterogeneous nature of enamel solubility. However, this range of values may also result from the variety of methods used, e.g., some authors reporting values for suspensions of enamel powder and others for bulk enamel. The aim of this study was to develop a method to measure the solubility of bulk human enamel under controlled in vitro conditions simulating demineralization behavior of enamel within the oral environment using scanning microradiography (SMR). SMR was used to monitor real-time changes in enamel demineralization rates at increasing calcium concentrations in a caries simulating demineralization solution until the concentration at which thermodynamic equilibrium between enamel and solution was achieved. Method: 2 mm thick caries free erupted human enamel slabs with the natural buccal surfaces exposed were placed in SMR cells exposed to circulating caries-simulating 2.0 L 0.1 M pH = 4.0 acetic acid, at 25°C. SMR was used to continuously measure in real-time the decrease in mineral mass during the demineralization at 5 different points from on each slab. Demineralization rates were calculated from a linear regression curve of projected mineral mass against demineralization time. Changes in the demineralization rates were monitored following a series of successive increases in calcium (and phosphate at hydroxyapatite stoichiometric ratios of Ca:P 1.67) were added to the demineralizing solution, until demineralization ceased. The pH was maintained constant throughout. Results: Demineralization halted when the calcium concentration was ~30 mM. At higher calcium concentrations, mineral deposition (remineralization) occurred. By comparison with results from speciation software calculations for the calcium phosphate ternary system, this result suggests that the bulk solubility product of enamel (pKspBEnamel) under the conditions used is 121. Discussion: The apparent pKspBEnamel under these conditions was higher than many previous reported values, and much closer to those previously reported for HAp. However, this is a bulk value, and does not reflect that enamel is a heterogeneous material, nor the influence of ionic inclusions.

Solubility products of sparingly soluble barium perborates in aqueous solution that contains B(OH)3 and H2O2 at 25°C.

Chemical oxo-precipitation (COP) has become a promising method for treating boron wastewater at room temperature; it uses hydrogen peroxide to convert boric acid to perborate species, which are precipitated using alkaline earth metals. In this work, solubility models of barium perborates were established to predict residual boron levels from COP. The solubility product constants (pKsp) of two major barium perborates - amorphous Ba(B(OH)3OOH)2 (A-BaPB) and crystalline BaB(OH)2(OO)2B(OH)2 (C-BaPB) - were experimentally estimated (8.335±0.109 and 9.190±0.057, respectively) to define the solubility curves of BaPBs at given pH, ionic strength and concentrations of barium and peroxide species. The characterization of precipitates that were formed by COP confirmed that the boron levels in aqueous solution were governed by the phase transformation of A-BaPB to C-BaPB. The predictive solubility models of barium perborates can perfectly predict the residual concentration of boron after COP treatment and can be used to optimize the process for reducing boron concentrations in wastewater.

Kinetics of the reversible reaction of struvite crystallisation.

The crystallisation of struvite could be a sustainable and economical alternative for recovering phosphorus from wastewater streams with high phosphate concentrations. Knowledge regarding the kinetics and thermodynamics that are involved in the crystallisation of struvite is the key to determine the optimal conditions for obtaining an efficient process. This study was conducted in a continuous stirred batch reactor. Different sets of experiments were performed in which struvite was either dissolved (undersaturated) or precipitated (oversaturated). These experiments were conducted at different temperatures (25, 30 and 35 °C) and pH values (8.2, 8.5 and 8.8) to determine the kinetics of struvite precipitation and dissolution. Struvite crystallisation was modelled as a reversible reaction. The kinetic rate parameters of struvite precipitation were 1.03·10(-4), 1.25·10(-4) and 1.54·10(-4) mol m(-2) min(-1) at 25, 30 and 35 °C, respectively. Similar kinetic rate parameters were determined for struvite dissolution. Struvite heterogeneous crystallisation can be represented by a first-order kinetic model that fitted well the experimental data.

Struvite crystallization under a marine/brackish aquaculture condition.

The results in this study show that struvite was formed in the digester at pH 7.7 due to the magnesium naturally present and the released ammonia and phosphate, resulting in low phosphate concentration in the digester. Apparently the digester already provided proper conditions for struvite formation. Under the brackish condition, the estimated thermodynamic solubility product and enthalpy change of struvite formation were 10(-13.06) and 25.7kJmol(-1), respectively. The average crystal size under marine/brackish condition decreased with pH, but increased with temperature. X-ray diffraction measurements indicate struvite (NH4MgPO4·6H2O) and dittmarite (NH4MgPO4·H2O) were predominant phosphorus species produced in filtrates of the digester. However, struvite and newberyite (HMgPO4·3H2O) were the predominant species precipitated from synthetic brackish waters after dosing MgCl2. It is pronounced that (waste)water characteristics played also an important role on the nature of phosphate precipitates. Under high NH4(+) condition, phosphorus precipitates containing ammonia were dominant, compared to other amorphous phosphates.