Tablet Samples Research Articles

Simultaneous Detection of Nalbuphine and Diclofenac as Important Analgesic Drugs in Biological and Pharmaceutical Samples Using a Pt:Co Nanostructure-Based Electrochemical Sensor

Nalbuphine (NB) and diclofenac (DF) are two important drugs for the relief of moderate to severe pain and determination of them are very important due to complications related to their overdose. A promising nanostructure modified electrode was fabricated by distributing Pt:Co nanoalloy (Pt:Co/NL) into carbon paste matrix in the presence of 1-methyl-3-butylimidazolium bromide (1M3BIBr) as a conductive binder. Energy-dispersive X-ray spectroscopy analysis (EDAX), transmission electron microscopy (TEM) and X-ray powder diffraction (XRD) were employed to confirm the synthesis of Pt:Co/NL by polyol method. The proposed sensor was applied to the simultaneous determination of nalbuphine (NB) and diclofenac (DF) in pH 7.0 phosphate buffer solution for the first time. The calibration curves for NB, and DF were obtained in the ranges of 0.05 to 1290 μM and 0.1 to 900 μM, respectively. The detection limits (3σ) were 9 nM and 50 nM for NB and DF, respectively. The interference study shows that the carbon paste electrode modified with Pt:Co/NL and 1M3BIBr (Pt:Co/NL/1M3BIBr/CPE) exhibits excellent selectivity for determination NB and DF in the presence of other biological specie. The 1M3BIBr was applied to ampule and tablet samples and excellent results were obtained.

Identification of l-carnitine and its impurities in food supplement formulations by online column-switching liquid chromatography coupled with linear ion trap mass spectrometry.

The identification of impurities in l-carnitine by mass spectrometry is difficult because derivative reagents or ion pair reagents are usually used to separate and increase the retention of l-carnitine on the reversed-phase column. In this study, four impurities including 3-chloro-2-hydroxy-N,N,N-trimethylpropan-1-aminium, 3-cyano-2-hydroxy-N,N,N-trimethylpropan-1-aminium, 3-carboxy-N,N,N-trimethylprop-2-en-1-aminium, and 4-chloro-2,3,4-trihydroxy-N,N,N-trimethylbutan-1-aminium were identified in l-carnitine and its tablets by using two-dimensional column-switching high-performance liquid chromatography coupled with linear ion trap mass spectrometry. The first column was a C8 column at a flow rate of 0.15 mL/min; the detection wavelength was 220 nm. The second column was an Acclaim Q1 column using a gradient elution program with aqueous 30 mM ammonium acetate (pH 5.0) and acetonitrile as the mobile phase at a flow rate of 0.5 mL/min. The mass fragmentation patterns and structural assignments of impurities were studied, and the quantitative validation of three impurities was further investigated. The linearity (r2 ) was found to be >0.99, with ranges from 0.2 to 50 ng/mL and 0.1 to 10 ng/mL. The method was used successfully for determination of impurities in five samples of l-carnitine and tablets.

29 Tablet form and color design method based on support vector regression and swarm intelligence

Objectives The emotional effect of a tablet’s form and color on patients can affect their choice of drug, and their confidence in the effect of treatment. In order to improve the drug’s treatment effect, it is necessary to design the tablet’s form and color to meet the patients’ emotional needs. This paper proposes a method for designing the form and color of tablets based on support vector regression and a swarm intelligence algorithm. Methods First, the method decomposes the design elements of the tablet, and assigns category labels and fuzzy affiliation values to tablet samples in order to build the classification model. The patients’ perceptions of tablet samples can be obtained through their subjective evaluation. The mapping model between design elements and patients’ perceptual images can then be built using a support vector regression model. Finally, the design scheme is optimized using a swarm intelligence algorithm. Results The proposed method can assist designers to quickly identify a satisfying design scheme despite limited options, and can increase the success rate of tablet design and improve treatment effect. Conclusions The proposed method can effectively produce a satisfying design scheme while accounting for different image preferences caused by individual differences. Therefore, this method can provide a valid approach for large-scale design and theoretical support for tablet design. Acknowledgments This research was financially supported by the National Natural Science Foundation of China (Grant No. 51575158) and Hebei Province Natural Science Foundation of China (Grant No. E2016202058).

Electrochemical Determination of Albendazole at Glassy Carbon Electrode.

In this article, the electrochemical behavior on a glassy carbon electrode (GCE) was investigated and the electrochemical parameters of albendazole (ALB) were calculated. ALB effectively accumulated on the GCE surface and caused a pair of redox peaks at around 1.095 V and 1.028 V and an oxidation peak at 0.844 V (versus saturated calomel electrode) in 0.2 M phosphate buffer solution (pH 3.0). Under optimized conditions, the anodic peak current was linear to the ALB concentration the range of 1.5 × 10-7 M to 4.0 × 10-5 M. The regression equation was: Ipa (10-6 A) = 0.79 [ALB] (μM) + 0.84 (R2 = 0.982). The detection limit 6.08 × 10-8 M was obtained. The proposed method was successfully used to determine ALB content in tablet samples, with satisfactory results.

In-Process Control Assay of Pharmaceutical Microtablets Using Hyperspectral Imaging Coupled with Multivariate Analysis.

Monitoring the amount of active pharmaceutical ingredient (API) in finished dosage form is important to ensure the content uniformity of the product. In this report, we summarize the development and validation of a hyperspectral imaging (HSI) technique for rapid in-line prediction of the active pharmaceutical ingredient (API) in microtablets with concentrations varying from 60 to 130% API (w/w). The tablet spectra of different API concentrations were collected in-line using an HSI system within the visible/near-infrared (vis/NIR; 400-1000 nm) and short-wave infrared (SWIR; 1100-2500 nm) regions. The ability of the HSI technique to predict the API concentration in the tablet samples was validated against a reference high-performance liquid chromatography (HPLC) method. The prediction efficiency of two different types of multivariate data modeling methods, that is, partial least-squares regression (PLSR) and principle component regression (PCR), were compared. The prediction ability of the regression models was cross-validated against results generated with the reference HPLC method. The results obtained from the PLSR models showed reliable performance for predicting the API concentration in SWIR region. The highest coefficient of determination (R2p) was 0.96, associated with the lowest predicted error and bias of 4.45 and -0.35%, respectively. Furthermore, the concentration-mapped images of PLSR and PCR models were used to visually characterize the API concentration present on the tablet surface. Based on these results, we suggest that HSI measurement combined with multivariate data analysis and chemical imaging could be implemented in the production environment for rapid in-line determination of pharmaceutical product quality.

A highly sensitive and selective electrochemical determination of non-steroidal prostate anti-cancer drug nilutamide based on f-MWCNT in tablet and human blood serum sample

A novel electrochemical sensor based on the functionalized multiwalled carbon nanotube (f-MWCNT) was successfully developed for the sensitive and selective determination of non-steroidal prostate anti-cancer drug nilutamide in tablet and blood serum samples. The f-MWCNT was prepared by the simple reflux method and characterized by the scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, X-ray powder diffraction (XRD) and fourier transform infrared spectroscopy (FT-IR). Interestingly, the f-MWCNT was exhibited a superior electrocatalytic activity towards the anti-cancer drug nilutamide when compared with pristine MWCNT and unmodified electrodes. Besides, the electrochemical sensor was revealed an excellent current response for the determination of nilutamide with wide linear ranges (0.01–21μM and 28–535μM), high sensitivity (11.023 and 1.412μA μM−1cm2) and very low detection limit (LOD) 0.2nM. The developed electrochemical sensor was showed an excellent selectivity even in the presence of electrochemically active biological substances and nitro aromatic compounds. Moreover, it manifested a good reproducibility and stability. In addition, the f-MWCNT modified glassy carbon electrode (GCE) sensor was successfully applied for the detection of nilutamide in tablet and blood serum sample.

Nanomolar simultaneous determination of tryptophan and melatonin by a new ionic liquid carbon paste electrode modified with SnO2-Co3O4@rGO nanocomposite

This work describes the development of a new sensor for simultaneous determination of tryptophan and melatonin. The proposed sensor was an ionic liquid carbon paste electrode modified with reduced graphene oxides decorated with SnO2-Co3O4 nanoparticles. The voltammetric oxidation of the analytes by the proposed sensor confirmed that the electrooxidation process undergoes a two-electron/one-proton reaction for melatonin and a two-electron/two-proton reaction for tryptophan in diffusion-controlled processes. Moreover, based on the excellent electrochemical properties of the modified electrode, a sensitive voltammetric method was used for individual and simultaneous determination of melatonin and tryptophan in the aqueous solutions. Under the optimized experimental conditions, a linear response obtained in the range of 0.02 to 6.00μmolL−1 with detection limits of 4.1 and 3.2nmolL−1 for melatonin and tryptophan, respectively. The prepared sensor possessed accurate and rapid response toward melatonin and tryptophan with a good sensitivity, selectivity, stability, and repeatability. Finally, the applicability of the proposed sensor was verified by evaluation of melatonin and tryptophan in various real samples including human serum and tablet samples.

A selective strategy for determination of ascorbic acid based on molecular imprinted copolymer of o-phenylenediamine and pyrrole

In this work, a novel approach for selective and sensitive detection of ascorbic acid (AA) was proposed combined molecularly imprinted polymers and electrochemical sensor. The molecularly imprinted sensor was prepared by cyclic voltammetry on pencil graphite electrode with pyrrole (Py) and o-phenylenediamine (o-PD) as functional monomers and AA as template molecule. The sensor was evaluated through scanning electron microscope (SEM) and square wave voltammetry (SWV). The factors affecting electrochemical response of sensor were investigated and optimized. Under the optimum conditions, the imprinted sensor exhibited good selectivity and stability. The linear range of the sensor was 1×10−6 to 1×10−3mol/L, meanwhile, the detection limit was 2.63×10−7mol/L (S/N=3). This molecularly imprinted sensor has been successfully used in AA determination in real tablet samples with good recovery.

Voltammetric paracetamol sensor using a gold electrode made from a digital versatile disc chip and modified with a hybrid material consisting of carbon nanotubes and copper nanoparticles

A composite consisting of carbon nanotubes (CNT) and copper nanoparticles (CuNPs) was prepared by a chemical reduction method, and its structure characterized by scanning electron microscopy, transmission electron microscopy energy dispersive spectroscopy and FT-IR spectrometry. The hybrid composite was deposited on the surface of a disposable gold electrode that was manufactured from a commercial digital versatile gold disc by a drop casting method. The electrochemical properties of the modified electrode were investigated by cyclic voltammetry and differential pulse voltammetry. The sensor showed an excellent electrocatalytic activity towards oxidation of paracetamol (PA). The calibration plot (with current typically measured at 0.41 V vs. Ag/AgCl) is linear in the 0.5 to 80 μM concentration range, and the detection limit is as low as 10 nM. The sensor was successfully applied to the determination of PA in spiked water and tablet samples where it gave recoveries ranging between 95.25 and 100.5 %.

Investigation of the binding of AuNPs-6-mercaptopurine and the sensitive detection of 6-mercaptopurine using resonance Rayleigh light scattering.

A highly sensitive method for the detection of 6-mercaptopurine (MP) by resonance Rayleigh light scattering (RLS) method was developed. Gold nanoparticles (AuNPs) were synthesized by a modified seed method and characterized using transmission electron microscopy (TEM). AuNPs were bound to MP via covalent bonding to form the MP-AuNPs complex, which increased the RLS intensity of MP at 347nm (increased by 65.7%). Under optimum conditions, the magnitude of the enhanced RLS intensity for MP-AuNPs was proportional to MP concentration in the range 0.0681-1.702μgmL-1 . The linear regression equation was represented as follows: ΔIRLS = 9.31 + 82.42c (r=0.9948). The limit of detection (LOD, 3σ) was 3.32ngmL-1 . The system was applied successfully to detect MP in pharmaceuticals. MP recoveries were 99.9-101.7% with a relative standard deviation (RSD) (n=5) of 0.59-0.77% for three synthetic samples, and 97.5-110.0% with an RSD of 0.98-2.10% (n=5) for tablet samples.

A comprehensive strategy in the development of a cyclodextrin-modified microemulsion electrokinetic chromatographic method for the assay of diclofenac and its impurities: Mixture-process variable experiments and quality by design

A comprehensive strategy involving the use of mixture-process variable (MPV) approach and Quality by Design principles has been applied in the development of a capillary electrophoresis method for the simultaneous determination of the anti-inflammatory drug diclofenac and its five related substances. The selected operative mode consisted in microemulsion electrokinetic chromatography with the addition of methyl-β-cyclodextrin. The critical process parameters included both the mixture components (MCs) of the microemulsion and the process variables (PVs). The MPV approach allowed the simultaneous investigation of the effects of MCs and PVs on the critical resolution between diclofenac and its 2-deschloro-2-bromo analogue and on analysis time. MPV experiments were used both in the screening phase and in the Response Surface Methodology, making it possible to draw MCs and PVs contour plots and to find important interactions between MCs and PVs. Robustness testing was carried out by MPV experiments and validation was performed following International Conference on Harmonisation guidelines. The method was applied to a real sample of diclofenac gastro-resistant tablets.

Electrochemical determination of diazepam in real samples based on fullerene-functionalized carbon nanotubes/ionic liquid nanocomposite

A modified electrode using fullerene-functionalized carbon nanotubes and ionic liquid (IL, 1-butyl-3-methylimidazolium tetrafluoroborate) has been applied for the determination of diazepam in real samples including serum, urine, and tablets. The properties of fullerene-functionalized carbon nanotubes and ionic liquid were characterized by transmission electron microscopy, scanning electron microscope, electrochemical impedance spectroscopy, and voltammetry. The experimental results confirmed that modified electrode with fullerene-functionalized carbon nanotubes and ionic liquid has good electrocatalytic activity toward the reduction of diazepam. The electrocatalytic current increases linearly with the diazepam concentration in the ranges of 0.3–700.0μM, and the detection limit is 87±2nM. The proposed electrode displayed excellent repeatability and long-term stability and it was satisfactorily used for determination of diazepam in real samples (commercially tablet, urine, and serum samples) with high recovery.

A new simple electrochemical Moxifloxacin Hydrochloride sensor built on carbon paste modified with silver nanoparticles

A new sensitive simple electrochemical sensor for Moxifloxacin Hydrochloride (MOXI) detection has been successfully performed. The sensor built on carbon paste (CP) modified with silver nanoparticles (AgNPs). AgNPs are biocompatible stable noble materials especially in biological sensing. The silver nanoparticles modified carbon paste electrode (SNMCPE) displayed high electrocatalytic activity towards oxidation of 1.0mM MOXI in Britton Robinson (BR) buffer of pH range (2.0–9.0). The techniques used to do this work are cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS). Surface characteristics were achieved using scanning electron microscopic (SEM) and Energy Dispersive X-Ray Analysis (EDX) techniques. The effect of changing MOXI concentration (7.0×10−7 to 1.8×10−4M) was studied in BR buffer (pH =7.4) at a scan rate of 50mV/s using SNMCPE. The detection and quantification limits were found to be 2.9×10−9M and 9.6×10−8M, respectively. In order to assess the applicability of MOXI detection method in real samples; this method was tested in Delmoxa tablet and human urine sample. Good sensible results were attained for MOXI detection.

Sensitive and selective electrochemical detection of artemisinin based on its reaction with p-aminophenylboronic acid

The electrochemical detection of artemisinin generally requires high oxidation potential or the use of complex electrode modification. We find that artemisinin can react with p-aminophenylboronic acid to produce easily electrochemically detectable aminophenol for the first time. By making use of the new reaction, we report an alternative method to detect artemisinin through the determination of p-aminophenol. The calibration curve for the determination of artemisinin is linear in the range of 2 μmol L−1 to 200 μmol L−1 with the detection limit of 0.8 μmol L−1, which is more sensitive than other reported electrochemical methods. The relative standard deviation is 4.83% for the determination of 10 μM artemisinin. Because the oxidation potential of p-aminophenol is around 0 V, the present method is high selective. When 40 μM, 90 μM and 140 μM of artemisinin were spiked to compound naphthoquine phosphate tablet samples, the recoveries are 107.6%, 105.4% and 101.7%, respectively. This detection strategy is attractive for the detection of artemisinin and its derivatives. The finding that artemisinin can react with aromatic boronic acid has the potential to be exploited for the development of other sensors, such as fluorescence artemisinin sensors.

Cyclodextrin- and solvent-modified micellar electrokinetic chromatography for the determination of captopril, hydrochlorothiazide and their impurities: A Quality by Design approach

A fast and selective capillary electrophoresis method has been developed for the simultaneous determination of the antihypertensive drugs captopril and hydrochlorothiazide and their related impurities in a combined dosage form. Method development was carried out implementing each step of Quality by Design workflow, the new paradigm of quality outlined in International Conference on Harmonisation Guidelines. Captopril is characterized by the lack of a strong chromophore and contains a proline-similar moiety, which gives rise to the presence of interconverting cis-trans isomers and leads to the possible interference between electrophoretic migration and reaction of isomerization. The scouting phase was dedicated to the investigation of several operative modes in order to overcome detection and isomerization issues. The best performances were obtained with sodium cholate-based micellar electrokinetic chromatography with the addition of n-butanol and γ-cyclodextrin. Critical quality attributes were represented by the critical resolution values and by analysis time. Critical process parameters were defined as temperature, voltage, concentration and pH of borate buffer, concentration of sodium cholate, n-butanol and γ-cyclodextrin. Screening experimental design was applied for investigating knowledge space. Response surface methodology pointed out several significant interaction effects, and with Monte-Carlo simulations led to map out the design space at a selected probability level. Robustness testing was carried out and a control strategy based on system suitability tests was defined. The selected working conditions gave a complete separation of the analytes in less than three minutes. The method was validated and applied to the analysis of a real sample of coformulation tablets.

Fabrication a new modified electrochemical sensor based on Au–Pd bimetallic nanoparticle decorated graphene for citalopram determination

This paper proposes a simple approach for sensing of citalopram (CTL) using gold–palladium bimetallic nanoparticles (Au–PdNPs) decorated graphene modified gold electrode. Au–PdNPs were deposited at the surface of a graphene modified gold electrode with simple electrodeposition method. The morphology and the electrochemical properties of the modified electrode were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), energy dispersion spectroscopy (EDS), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV). The novel sensor exhibited an excellent catalytic activity towards the oxidation of CTL. The oxidation peak current of CTL, was linear in the range of 0.5–50μM with a detection limit 0.049μM with respect to concentration of citalopram. The proposed sensor was successfully applied for determination of CTL tablet and human plasma samples with satisfactory results.

Ionic liquid-β-cyclodextrin polymer for the separation/analysis of lornoxicam

Ionic liquid-β-cyclodextrin polymer (ILs-β-CDCP) was firstly synthesised and characterised with FTIR, 13C CP/MAS NMR, X-ray powder diffraction, TGA and scanning electron microscope. A novel method of solid phase extraction (SPE) coupled with Ultraviolet–vis spectrophotometry for separation/analysis of lornoxicam was established. ILs-β-CDCP showed a higher adsorption capacity towards lornoxicam than β-CDCP. Adsorption mechanism of ILs-β-CDCP was elucidated by adsorption thermodynamics model, adsorption kinetic model, inclusion constants and FTIR analysis. ILs-β-CDCP exhibited favourable adsorption performance towards lornoxicam from serum and tablet samples. The experimental results herein suggested that ILs-β-CDCP could be successfully applied in the field of pharmic content especially in the treatment of serum.

Oxidative stability of omega‐3 tablets

Preparing solid formulations, as powder and tablets, containing omega‐3 can be challenging as the necessary production processes expose the unsaturated omega‐3 fatty acids to high temperatures, light, and mechanical stress in presence of air. The present work demonstrates that omega‐3 tablets can be prepared with sufficiently low total oxidation values (totox) to satisfy relevant monographs for omega‐3 products. The tablets were prepared from spray granulated direct compaction grade 30% w/w triglyceride powders as characterized by Vestland, Jacobsen, Sande, Myrset, and Klaveness, 2015 (Food Chem. 2015. 185: p. 151–158; Food Chem., 2016. 197, Part A: p. 496–502). Addition of ascorbic acid, in combination with EDTA as processing agent, was correlated with lower totox in powders. Spray granulation performed under nitrogen atmosphere contributed to significantly decreased totox in powders after 8 months of storage at accelerated temperature (37°C) compared to spray granulation in air. In long‐term stability studies, it was confirmed that coated omega‐3 tablets remained at totox <5 after 1 year of storage at ambient temperature.Practical applications: The confirmation that oxidative stable omega‐3 tablets can be produced opens the possibility for a new administration form in the omega‐3 field. The use of dry powders in the production process imply more opportunities within combination products as dry powders typically exhibit fewer compatibility issues. Omega‐3 tablets are a gelatin‐ and lactose‐free alternative for health conscious individuals all over the world.The most frequently used formulation form for health supplements is tablets, however, to date there have been numerous issues with achieving sufficient oil load and maintain oxidative stability trying to formulate omega‐3 oil in tablets. Totox 26 is the limit set by the Global Organization for EPA and DHA (GOED) for omega‐3 supplement for human use (yellow line). As presented in this figure, omega‐3 tablets with 30% w/w triglyceride oil load (60% concentrate) have been prepared and totox have maintained lower than 26 for tablets kept at 37°C for 1 year. The data so far obtained from the long‐term stability study (tablet samples kept at ambient conditions) indicate the possibility for a +3 years shelf life for the omega‐3 tablets.

Preparation of Au nanoparticles decorated polyaniline nanotube and its catalytic oxidation to ascorbic acid

With sulfonated electrospun polystyrene fiber as a template, uniform polyaniline(PANI) nanotubes were fabricated via polymerization of aniline followed by template removal. Au nanoparticles(Aunano) were decorated on the PANI nanotube successfully via auto-reduction of HAuCl4 on the PANI nanotube. The morphology of the nanotubes was characterized by means of scanning electron microscopy(SEM) and transmittance electron microscopy(TEM). By varying precursor concentration and incubation time, Aunano-PANI with different size of Aunano was obtained conveniently. Glassy carbon electrode modified with the Aunano decorated PANI nanotubes (Aunano-PANI/GCE) was prepared and used seccessfully for the catalytic oxidation of ascorbic acid(AA). The results of differential pulse voltammetry indicate that there is a good linear relationship between the peak currents and the concentrations of AA in the range of 5―3000 μmol/L, with the limit of detection of 1 μmol/L(S/N>3). There is no mutual interference between AA and dopamine. The electrode has been successfully applied in the detection of AA in vitamin C tablet sample.

Simultaneous determination of nineteen major active compounds in Qiangshen tablet by UPLC-ESI-MS/MS

An ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry method has been developed to evaluate the quality of a pharmaceutical herbal preparation, Qiangshen tablet, through a simultaneous determination of 19 major active compounds (stachydrine hydrochloride, betaine, gallic acid, sodium danshensu, morroniside, loganin, protocatechuic aldehyde, gardenoside, sweroside, acteoside, paeoniflorin, ginsenoside Re, rosmarinic acid, salvianolic acid B, ginsenoside Rg1, psoralen, isopsoralen, ginsenoside Rb1, paeonol). Chromatographic separation was achieved on an ACQUITY UPLC® BEH C18 column (2.1×100mm, 1.7μm) by gradient elution with the mobile phase of 0.1% formic acid aqueous solution (A) and acetonitrile (B). Multiple reaction monitoring (MRM) mode with positive and negative electrospray ionization interface was operated to detect the 19 compounds. All calibration curves showed excellent linear regressions (r>0.999) within the test range. The precision, repeatability and stability of the 19 compounds were below 2.0% in terms of RSD. The recoveries were 97.5–102.2% with RSD of 1.0–1.9% for Qiangshen tablet samples. The method was successfully used for the analysis of samples of Qiangshen tablet. In conclusion, a rapid, sensitive, precise, accurate and reliable UPLC-ESI-MS/MS method has been developed for the simultaneous detection of 19 active compounds with large difference in level of content in the pharmaceutical samples of Qiangshen tablet, which can be applied for the quality control of Qiangshen tablet.