Acid-base Neutralization Method Research Articles

Formulation and Evaluation of Nano Suspension Based Oro Disoersible Film of Aripiprazole

The present study was aimed to enhance the solubility and dissolution of BCS class 4 drug aripiprazole, by nano formulation approach. Acid-base neutralization method had been used to produced nanosuspension. The nanosuspensions remained stable without any aggregations with particle size 209.6nm and PDI 0.247. Zeta potential was found to be 3.5mV. Drug content, Entrapment and solubility of nanosuspension formulations were determined. In vitro drug release of the selected formulation has shown a drug release of 95.63% by the end of 1 hr, whereas plain drug suspension has shown only 12.3% release. XRD and DSC studies revealed that the solid form of aripiprazole altered from the crystalline state to the amorphous state after incorporation into nanosuspensions. Hence, from the results, it can be concluded that Aripiprazole, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability

Acid-base neutralization strategy for immobilization amino acid ionic liquid within sulfonic acid-based COF as a switch for selective conversion of epoxides

Covalent organic frameworks (COFs) and ionic liquids (ILs) as raw materials exhibit effective catalytic performance and adsorption capabilities in the reaction of epoxides and atmospheric CO2, respectively. Nonetheless, bonding modes between ILs and COFs have restricted their utility, thereby constraining the in-depth study of synergistic catalytic mechanisms over these composite catalysts. Herein, a heterogeneous composite ([DBUH]2Cys@COF-X) were successfully prepared by the facile acid-base neutralization method, incorporating varying amounts of amino acid ILs ([DBUH]2Cys) into the pore channels of sulfonic acid-based COF (TpPa-SO3H). [DBUH]2Cys@COF-3 efficiently catalyzed epichlorohydrin with a yield of 96.38 % without any solvent or co-catalyst under atmospheric CO2. Notably, larger sterically hindered epoxides were selectively blocked on the surface of [DBUH]2Cys@COF-3, enabling [DBUH]2Cys@COF-3 to act as a gatekeeper for selectively catalyzing small sterically hindered epoxides due to [DBUH]2Cys was distributed within the pore channels of [DBUH]2Cys@COF-3. Through DFT calculations, comprehensive understanding of the synergistic activation conferred of -COO- and [DBUH]+ towards CO2 and epoxides in [DBUH]2Cys@COF-3 and the ring-opening mechanism was clarified. This work presents a fresh outlook on the catalyst design by the facile acid-base neutralization method for efficiently catalyzing small-hindered epoxides under atmospheric CO2.

Optimization of Desulfurization Process via Choline Phosphotungstate Coupled with Persulfate Using Response Surface Methodology

Using a simple acid-base neutralization method, a Ch-PW solid catalyst was synthesized by mixing choline hydroxide (ChOH) and phosphotungstic acid (HPW) at a 2:1 molar ratio in an aqueous solution. This catalyst was combined with a 20 wt.% potassium peroxymonosulfate (PMS) solution, using acetonitrile (ACN) as the extraction solvent to create an extraction catalytic oxidative desulfurization system. The optimal desulfurization conditions were determined through response surface methodology, targeting the highest desulfurization rate: 0.99 g of Ch-PW, 1.07 g of PMS, 2.5 g of extraction solvent, at a temperature of 50.48 °C. The predicted desulfurization rate was 90.79%, compared to an experimental rate of 93.64%, with a deviation of 3.04%. A quadratic model correlating the desulfurization rate with the four conditions was developed and validated using ANOVA, which also quantified the impact of each factor on the desulfurization rate: PMS > ACN > Ch-PW > temperature. GC-MS analysis identified the main oxidation product as DBTO2, and the mechanism of desulfurization in this system was further explored.

CO2 absorption using two morpholine protic ionic liquids: measurement, model, and quantum chemical calculation

Two kinds of protic ionic liquids, N-methylmorpholinium formate ([NMMH][For]) and N-ethylmorpholinium formate ([NEMH][For]), were synthesized by the acid-base neutralization method. The solubility of carbon dioxide (CO2) in the two ionic liquids was measured at temperatures of 298.15 to 338.15 K and pressures of up to 900 kPa. The solubility increases linearly with pressure, indicating that CO2 is physically absorbed in ionic liquids. The solubility of CO2 in [NEMH][For] is higher than that of [NMMH][For]. Absorption behavior was investigated by thermodynamic properties, such as the Henry's law constant, partial molar Gibbs free energy, partial molar enthalpy, and partial molar entropy. The Pitzer's model and the Soave-Redlich-Kwong (SRK) cubic equation of state were used to fit the solubility data, respectively. The Pitzer's model is found to have better prediction accuracy. The interaction of two protic ionic liquids with CO2 was analyzed using quantum chemistry. The molecular mechanism of CO2 absorption by two protic ionic liquids was explained from the microscopic point of view. CO2 + [NEMH][For] has more hydrogen bonds and a higher interaction energy. The cation–anion interaction of [NEMH][For] diminishes in the presence of CO2, resulting in an increase in the cation–anion distance. These factors result in higher solubility of CO2 in [NEMH][For].

Preparation of nanocomposite material based on Porphyrin and electrochemical analysis for green fuel production

In the current environmental pollution situation, using green fuel sources such as H2 gas to overcome the challenge of pollution and resource depletion is a useful solution. This research used the acid-base neutralization method with the recombination process to successfully fabricate CuFe2O4/TCPP nanocomposites. The morphological and structural properties of the materials were evaluated by scanning electron microscopy (SEM), X-ray diffraction (XRD) which show that the resulting material has a structure consisting of TCPP filaments with a diameter of about 20-30 nm and a length of µm, interspersed with CuFe2O4 particles with sizes in the range of 100 nm. The electrochemical properties of the as-prepared material film were investigated by Cyclic Voltammetry (CV) and electrochemical impedance spectroscopy (EIS) on a glassy carbon electrode with a 3-electrodes system. The results show the appearance of electrochemical characteristics of copper ferrite/porphyrin hybrid materials and especially the change of electrochemical characteristics when this nanocomposite was irradiated by an external light source. These results are expecting to apply this material in the photocatalytic process to produce green fuel H2 from water.

Design and evaluation of in vivo bioavailability in beagle dogs of bilayer tablet consisting of immediate release nanosuspension and sustained release layers of rebamipide

The purpose of this study was to develop a once-daily, bilayer matrix tablet with immediate (IR) and sustained release (SR) layers of poorly water-soluble and absorption site dependent rebamipide (RBM) to substitute three times a day IR tablet. Owing to the pH-dependent poor water solubility of RBM in low pH condition, salt-caged nanosuspensions (NSPs) consisting of RBM and poloxamer 407 (POX 407) or poloxamer 188 (POX 188) were prepared using an acid-base neutralization method to increase the dissolution rate, which was subsequently applied to the immediate-release (IR) layer. Polyethylene oxide (PEO) with different molecular weights (PEO 100,000 and PEO 5,000,000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were then investigated as SR agents to incorporate into the SR layer with pure RBM via wet granulation method. The dissolution profile of the optimized bilayer tablet having 50% IR and 50% SR layer of 300 mg RBM showed that the IR layer could rapidly disintegrate in pH 1.2 buffer solution within 2 h, reaching 50% of drug release from the tablet, followed by an extended drug release from the SR layer in pH 6.8 buffer over 24 h. An in vivo pharmacokinetic study was carried out in beagle dogs to compare the optimal formulation (300 mg RBM bilayer tablet) and the commercial tablet (Mucosta® 100 mg) as a reference. Unexpectedly, despite enhanced dissolution rate in a controlled manner, a designed bilayer tablet had no dose- and dosage form dependent in vivo bioavailability in beagle dogs as compared with IR 100 mg RBM reference tablet. It was evident that solubility in low pH condition, gastric residence time and absorption site of RBM should be carefully considered for designing specific SR or gastroretentive dosage form to improve therapeutic outcomes.

Biocompatible anions-derived ionic liquids a sustainable media for CO2 conversion into quinazoline-2,4(1H,3H)-diones under additive-free conditions

Based on an one-step acid-base neutralization method, several biocompatible anions-derived ionic liquids (bio-AILs) were prepared and characterized. They were first used as dual solvent-catalyst for cyclization of CO2 and 2-aminobenzonitriles to synthesize quinazoline-2,4(1H,3H)-diones. The influence of different bio-AILs structures on the cyclization reaction were studied, and [HTMG][Lae] was confirmed to be an excellent medium. By optimizing the reaction conditions, the [HTMG][Lae]-mediated cyclization reaction could afford a 96 % quinazoline-2,4(1H,3H)-dione yield at 70 °C, 1.0 MPa CO2 pressure for 6 h without other additives. The catalytic activities of various homogeneous media for transformation of CO2 into quinazoline-2,4(1H,3H)-dione were analyzed and compared. In addition, the reusability and general applicability of the [HTMG][Lae] medium were examined, the [HTMG][Lae] could show comparable activity in the fifth experiment, and it had good versatility for cyclization of CO2 with various 2-aminobenzonitriles. Finally, an insight into the activation behaviors of [HTMG][Lae] to reactants were further investigated, and based on this, a feasible reaction mechanism was proposed.

Synthesis and evaluation of the cancer cell growth inhibitory activity of the ionic derivatives of oleanolic acid and ursolic acid with improved solubility

Formation of ionic derivatives from drugs provided a simple tool to tune physical properties including water solubility and biological activity of the drugs. Oleanolic acid (OA) and ursolic acid (UA) are two ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. But the poor water solubility greatly limits their clinical application. In order to improve the solubility of OA and UA, this research exploited a non-covalent synthetic approach to prepare a series of novel ionic derivatives of OA and UA by a simple acid-base neutralization method for converting them into simple organic salts. The OA/UA based ionic derivatives were characterized by HRMS, FTIR, NMR, XRPD, and TGA-DSC, their solubilities and apparent 1-octanol/water partition coefficients were measured under different conditions. The solubility of the ionic derivatives turned out to be higher than that of OA/UA under most of experiment conditions, which indicated our aim to improve the solubility was attained. The apparent 1-octanol/water partition coefficients indicated that the ionic derivatives of OA/UA had higher hydrophilicity than OA/UA under most of the experiment conditions. Moreover, the human hepatoma cell lines (HepG2) growth inhibitory activity of the derivatives was also evaluated by MTT assay. The results suggested that UA based ionic derivatives exhibited significantly lower IC50 values than OA based ionic derivatives under the same conditions, indicating stronger inhibitory effect on the growth of HepG2 cells.

A Design of Experiment (DoE) based approach for development and optimization of nanosuspensions of telmisartan, a BCS class II antihypertensive drug

BackgroundThe present study was aimed to enhance the solubility and dissolution of BCS class II drug, telmisartan (TEM), by nanoformulation approach. Several attempts were made to develop a nanosuspension by bottom-up and top-down techniques. In our study, we found in situ nanoamorphization technique to be incompatible and hence was not selected for further development of nanoformulation. Bottom-up techniques such as anti-solvent precipitation and emulsification solvent evaporation methods failed to reduce the size of the drug to nanoform by HPMC E15 and PVP K-25 at 1500–2000 rpm but resulted in micron-sized particles.ResultsHowever, the acid-base neutralization method has produced nanosuspension with a particle size of 243.9 nm and 0.119 PDI. Formulation and analytical development were carried out by statistical factorial design using the Design-Expert software (version 11.0). The nanosuspensions remained stable even after 90 days without any aggregations with particle size 338.1 nm and PDI 0.146. Zeta potential of optimized formulation was found to be − 16.2 mV. Drug content and its release were estimated by the developed and validated in-house HPLC method. In vitro drug diffusion studies on the optimized formulation have shown a drug release of 82.6% by the end of 3 h, whereas plain drug suspension has shown only 42.8% release, indicating a 2-fold increase of drug diffusion with nanosuspension. Ex vivo drug permeation studies performed using excised goat gastric mucosa revealed much faster permeation of TEM from nanosuspension than the plain drug suspension.ConclusionsHence, from the results, it can be concluded that TEM, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability.

An ultra-selective fluorescence method with enhanced sensitivity for the determination of manganese (VII) in food stuffs using carbon quantum dots as nanoprobe

A novel fluorescence method was for the first time established for the efficient determination of permanganate (Mn(VII)) based on sulfur, chlorine and nitrogen co-doped carbon quantum dots (S,Cl,N-CQDs). The S,Cl,N-CQDs was prepared via a fast and simple acid-base neutralization method. The fluorescence of S,Cl,N-CQDs could be dramatically quenched by Mn(VII) ascribed to a combination of inner filter effect (IFE) and dynamic quenching. Under the optimal working conditions, the S,Cl,N-CQDs-based nanoprobe exhibited high selectivity and sensitivity towards Mn(VII) sensing. A good linear Stern-Volmer equation was obtained for Mn(VII) in a wide concentration range of 0.05–110 μM with a detection limit as low as 12.8 nM. The proposed fluorescence method also exhibits additional advantages of great simplicity, fast in analysis and low cost. The as-fabricated fluorescent nanoprobe was successfully applied for the determination of Mn(VII) in vegetable, cereal and tea samples with high accuracy. It is anticipated that the S,Cl,N-CQDs-based nanoprobe could be further exploited to construct a nanoprobe device for Mn(VII) monitoring in complex food matrix.

A sensitivity enhanced fluorescence method for the detection of ferrocyanide ions in foodstuffs using carbon nanoparticles as sensing agents

A novel fluorescent nanoprobe was for the first time developed for the efficient detection of ferrocyanide ions ([Fe(CN)6]4−) based on nitrogen (N), sulfur (S) and chlorine (Cl) co-doped carbon nanoparticles (N,S,Cl-CNPs). The N,S,Cl-CNPs were fabricated through a simple and ultrafast acid-base neutralization method. The sensing mechanism was based on the quenching effect of [Fe(CN)6]4− on the fluorescence emission of N,S,Cl-CNPs via dynamic interaction. The N,S,Cl-CNPs were found to show high selectivity and sensitivity towards [Fe(CN)6]4− detection with two good linear relationships were achieved in the concentration ranges of 0.01–1.0 μg/mL and 1.0–50.0 μg/mL, respectively, and the detection limits are as low as 3.3 and 21.8 ng/mL, respectively. The proposed fluorescence method was successfully applied for [Fe(CN)6]4− analyses in food samples with high accuracy. The results of this study indicate the great application prospects of N,S,Cl-CNPs for [Fe(CN)6]4− detection in complex food matrix.

In situ immobilization of layered double hydroxides onto cotton fiber for solid phase extraction of fluoroquinolone drugs

Cotton fiber was proposed as a biodegradable support material. The properties like high specific area, hygroscopicity and adjustable shape make it be an idea substrate for solid phase extraction (SPE). In this work, inorganic layered double hydroxides (LDHs) were in situ immobilized onto cotton fiber through the linker of polydopamine as stationary phase. Uniform NiAl-LDHs crystal with nanostructure was observed on cotton fiber after one-step synthesis through urea hydrolytic method. The cotton fiber can not only increase the specific area and mass transfer rate, but also prevent aggregation and blocking of the freestanding LDHs crystal. Due to the electrostatic interaction and anion exchange features of LDHs, the prepared LDHs modified cotton fiber showed good extraction efficiency and selectivity towards fluoroquinolone drugs including norfloxacin, ciprofloxacin and enrofloxacin. After elution by 1 M NaOH, a simple acid-base neutralization method was proposed, so the natural elution can be directly analyzed by HPLC system. After optimizing the extraction parameters including adsorbent amount, sampling rate, sample volume, sample pH and eluent types and concentration, excellent extraction efficiency towards three fluoroquinolone drugs was obtained with high enrichment factors of 37–47. The adsorption capacity of LDHs modified cotton fiber was 21.18, 21.85 and 20.54 mg g−1 for norfloxacin, ciprofloxacin and enrofloxacin, which was almost twice as much as that of freestanding LDHs. The established method based on SPE-HPLC-FLC (fluorescence detector) technique exhibited good linearity (R2 ≥ 0.995), low limits of detection (0.01 µg L−1) and good reproducibility (intra-day RSDs ≤ 3.89%). Moreover, this method has also been applied in analyzing fluoroquinolone drugs in chicken eggs and pork liver.

Development of a fast dissolving sublingual film containing meloxicam nanocrystals for enhanced dissolution and earlier absorption

The objective of this work was to prepare and evaluate fast dissolving sublingual films containing meloxicam nanocrystals (MLX-NS-FDSFs). Nanocrystals (NS) were utilized to allow for improved dissolution of the drug, whereas the films were used to shorten the onset of action via the sublingual route. Meloxicam nanocrystals (MLX-NS) were prepared by nanoprecipitation based on acid-base neutralization method and then encapsulated into the films by solvent casting method. The obtained FDSFs exhibited uniform thickness of 82 ± 8 μm and drug content of 7.38 ± 0.011 mg/film (4 cm2) and disintegrated rapidly in 23.08 ± 1.76 s. The MLX-NS-FDSFs with reconstituted particle size of 196.4 ± 6.3 nm showed faster dissolution rate in vitro than the MLX coarse suspension based films (MLX-CS-FDSFs). The SEM images and XRD indicated that MLX nanocrystals were highly dispersed into the films. After administrated to rats, Tmax of MLX was significantly shortened following sublingual administration of MLX-NS-FDSFs. The absorption of MLX from MLX-NS-FDSFs resulted in 3.00 fold increased in bioavailability as compared to MLX-CS-FDSFs and 4.34 times with reference to the MLX-CS. These results indicated that the NS-FDSFs could be a promising delivery system to enhance the dissolution and shorten the onset time of MLX.

Layered double hydroxides based ion exchange extraction for high sensitive analysis of non-steroidal anti-inflammatory drugs

Layered double hydroxides (LDHs) are ideal sorbents for solid phase extraction (SPE) because of the excellent ion exchange capacity and high specific surface area. However, difficult elution of the analytes from the LDHs is a problem due to the strong ionic interaction between anions and LDHs. High concentrated NaOH solution is employed to elute the sample, but it not suitable for analyzing by HPLC. To solve this problem, a simple acid-base neutralization method was proposed after elution, and then the neutral samples were directly injected to HPLC for analysis. Nickel-aluminum layered double hydroxides (NiAl-LDHs) were synthesized by co-precipitation method and packed into a micro pipette tip for the extraction of three non-steroidal anti-inflammatory drugs (NSAIDs) including ketoprofen, naproxen and flurbiprofen from aqueous samples. After optimization of the experimental parameters such as the concentration of the NaOH, sample pH, sampling rate and sample volume, excellent extraction efficiency towards three NSAIDs was obtained with high enrichment factors of 28–32. A NiAl-LDHs based SPE-HPLC method was developed for quantitative analysis of NSAIDs, and the method showed low limits of detection (0.002–0.1ng/mL), good linearity (R2≥0.9995) and good reproducibility (intraday RSD≤4.37%). The developed method was also applied to the analysis of three NSAIDs in spiked human plasma and rat plasma after oral administration, which demonstrated the practicality of the proposed method.

Preparation of tetrafluoroethylene from the pyrolysis of pentafluoropropionate salts

The use of tetrafluoroethylene (TFE) in academic institutions beyond a few millimoles has often been inhibited by the compound's inherent danger and general lack of commercial availability. On the other hand, TFE is prepared industrially on a rather large scale by a number of major fluorochemical companies via the pyrolysis of chlorodifluoromethane at high temperatures, yielding TFE and HCl. For a few years at The University of Alabama and Clemson University, we have been preparing TFE on a 100+-gram scale by the pyrolysis under dynamic vacuum of pentafluoropropionate salts, which can be obtained from the neutralization of pentafluoropropionic acid with a M(OH)n (where M=Li, Na, K, and Cs for n=1 and Mg, Ca, and Ba for n=2). Additionally, potassium pentafluoropropionate can be prepared from the reaction of potassium trimethylsilanolate and ethyl pentafluoropropionate. The pentafluoropropionate salts and their decomposition products have been characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), accelerating rate calorimetry (ARC), nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, Fourier transform-infrared (FTIR) spectrophotometry, scanning electron microscopy (SEM)/energy dispersive spectroscopy (EDAX), X-ray diffraction (XRD), and single-crystal X-ray crystallography, where applicable. Typical yields of TFE obtained from pyrolysis of potassium pentafluoropropionate obtained from the acid-base neutralization method are >98%, while yields of TFE from the same salt prepared by the silanolate method from ethyl pentafluoropropionate are ca. 80%.

Modeling and Characterization of Steam-Activated Carbons Developed from Cotton Stalks

Abstract Physically and chemically activated carbons (ACs) exhibited high adsorption capacities for organic and inorganic pollutants compared with other adsorbents due to their expanded sur-face areas and wide pore volume distribution. In this work, seven steam-ACs with different burn-off have been prepared from cotton stalks. The textural properties of these sorbents were determined using nitrogen adsorption at -196°C .The chemistry of the surface of the present sorbents was characterized by determining the surface functional C-O groups using Fourier transform infrared spectroscopy, surface pH, pH pzc , and Boehm’s acid-base neutral-ization method. The textural properties and the morphology of the sorbent surface depend on the percentage of burn-off. The surface acidity and surface basicity are related to the burn-off percentage. A theoretical model was developed to find a mathematical expression that relates the % burn-off to ash content, surface area, and mean pore radius. Also, the chemistry of the carbon surface is related to the % burn-off. A mathematical expression was proposed where % burn-off was taken as an independent factor and the other variable as a dependent factor. This expression allows the choice of the value of % burn-off with required steam-AC properties.

Hybridization of layered niobates with cationic dyes

The hybridization of two different types of organic polycations, 1,1’-dimethyl-4,4’-bipyridinium dications (methyl viologen, MV2+) and 5,10,15,20-tetrakis(N-methyl-pyridinium-4-yl)-21H,23H-porphine tetracations (TMPyP4+), into layered niobates was investigated to construct an efficient dye-modified semiconductor for solar conversion and storage. Two different methods were employed for the direct intercalation of the cationic species, i.e., conventional ion-exchange with K4Nb6O17 · 3H2O as the starting host and a novel acid-base neutralization method with H4Nb6O17 as the starting host. These two methods showed totally different behavior and the characteristic features of both will be discussed in relation to the structure of the hybrid formed, the amount of absorption observed for the guest molecules and the intercalation rates. An analysis of the photo-induced electron-transfer reactions will also be discussed to show how control of the intercalation of guest molecules affects the photofunctionality of these unique hybrids.

Preliminary evaluation of bubble column flocculation

Experiments were carried out to determine the efficacy of bubble column flocculation. An acid-base neutralization method was used to determine the mixing time in a 0.064- by 1.5-m bubble column equipped with a Mott porous sparger. The mixing times decreased as the tracer injection point approached the gas sparger. Preliminary flocculation experiments on two clay samples were carried out. The effects of frother addition and airflow rate are presented and discussed.