Co-formulated Drugs Research Articles

New chemometrics-assisted spectrophotometric methods for simultaneous determination of co-formulated drugs montelukast, rupatadine, and desloratadine in their different dosage combinations

Two accurate, precise and robust multivariate chemometric methods were developed for the simultaneous determination of montelukast sodium (MON), rupatadine fumarate (RUP) and desloratadine (DES). These methods provide a cost-effective alternative to chromatographic techniques by utilizing spectrophotometry in pharmaceutical quality control. The proposed approaches, partial least squares-1 (PLS-1) and artificial neural network (ANN), were optimized using genetic algorithm (GA) to select the most influential wavelengths, enhancing model performance. A five-level, three-factor design was employed to construct a calibration set with 25 mixtures, utilizing concentration ranges of 3–19, 5–25, and 4–20 µg.mL−1 for MON, RUP, and DES, respectively. An independent validation set was employed to assess the performance of the models. GA significantly improved the PLS-1 and ANN models for RUP and DES, though minimal enhancement was observed for MON. These methods were successfully applied to the simultaneous quantification of the compounds in pharmaceutical formulations and proved useful as stability-indicating assays for RUP, given that DES is a known degradation product. The developed methods offer a valuable tool for impurity profiling and quality control in pharmaceutical analysis.

Novel quantum dots-based assay for the determination of anti-hypertensive drugs minoxidil and timolol in different matrices

The present work reports a sensitive, affordable, and ecologically friendly spectrofluorimetric method for the assessment of two antihypertensive medications, namely minoxidil and timolol. Blue-emitting sulfur and nitrogen co-doped carbon quantum dots (S,N-CQDs) were generated by exposing soluble starch and thiourea to a 15-minute microwave treatment. The so- prepared nanodots displayed fluorescence at 276/430 nm with a quantum yield of 22 %. Inspection of the so-prepared nano-sensor verified their doping with nitrogen and sulfur, and their size was in the range of 4.5–9.03 nm. The proposed method was found to be rectilinear in the range of 0.20–5.0 and 2.0–30.0 µg/mL, with LOQs of 0.16 and 0.82 µg/mL for minoxidil and timolol, respectively. The developed method was employed to assess the concentrations of minoxidil and timolol in their pharmaceutical formulations, with %recoveries varying between 99.00 % and 101.94 %, and low RSD values (less than 2 %). The high sensitivity of the developed method allowed its use for timolol measurement in artificial aqueous humor, with % recoveries between 97.60 %.and 101.57 %. The study further examined how each analyte interacted with the prepared dots, leading to a quenching of their fluorescence. Additionally, an interference study was utilized to evaluate the specificity of the proposed approach through determining analyte levels in the existence of common additives, co-formulated drugs, and co-administered drugs. The analytical eco-scale, GAPI and AGREE assessment techniques were utilized to confirm the suggested method greenness.

Implementation of quality by design approach for optimization of the green voltammetric analysis of a brain doping agent (Piracetam) using a novel molecular imprinted polymeric sensor

It is encouraging to note that in recent years there has been a growth of high-quality articles detailing molecular imprinted sensors for the detection of biomolecules, illicit narcotics, and explosives, paving the way for the technology’s usage in forensic and medical diagnostics.Thus in this work, a molecularly imprinted polymeric sensor was fabricated, for the first time, for the sensitive and selective determination of a brain doping agent; Piracetam, using a pencil-graphite electrode. This sensor was created by the simple anodic electro-polymerization of o-phenylenediamine (o-PD) with Piracetam as the template. Then the sensor was activated by removing the template using a suitable solvent mixture. Because of Piracetam’s lack of electro-activity, [Fe (CN)6]3−/4− has been used as an electrochemical probe that produces analytically relevant voltammetric signals by competing for the binding sites. Based on UV-spectrophotometric measurements, Job’s approach confirmed the expected stoichiometric ratio between Piracetamand the chosen monomer. X-ray photoelectron spectroscopy and cyclic voltammetry techniques were used for the characterization of the fabricated sensors. Different factors affecting the electro-polymerization conditions as; the effect of scan rate, number of cycles, pH of electro-polymerization, and the incubation time for rebinding were studied and optimized using fractional factorial design, in which the predicted model fits well to the experimental data as proved by ANOVA results. The developed voltammetric platform was applied for the in-line quantification of Piracetam in its pure solutions, pharmaceutical dosage form, and spiked human plasma with high accuracy and selectivity without the interference of the co-formulated drug; Citicoline sodium and excipients. The proposed molecular imprinted sensor was very sensitive with a linearity range (1.00 × 10−13 − 1.00 × 10−12 M), with LOD down to 4.38 × 10−15 M. This method was statistically compared with the reported method, and no statistically significant difference was found. The proposed method was assessed for greenness quantitatively and qualitatively using the Green Analytical Procedure Index (GAPI) and Analytical GREEnness metric (AGREE) as new greenness assessment tools.

Bioinspired Carbon Dots-Based Fluorescent Sensor for the Selective Determination of a Potent Anti-Inflammatory Drug in the Presence of Its Photodegradation Products.

Herein, we synthesized biogenic carbon dots (CDs) with blue-shifted maximum excitation (λex/λem of 320/404 nm) from largely wasted tangerine seeds for the first time via a one-step hydrothermal method. The biogenic CDs exhibit a maximum excitation wavelength that overlaps with the absorption spectrum of ketorolac tromethamine (KETO) at 320 nm. The developed CDs serve as a turn-off fluorescent probe via an inner filter effect (IFE) quenching mechanism. The resulting CDs have high quantum yield (QY) (39% ± 2.89%, n = 5) and exhibited great performance toward KETO over a concentration range of 0.50-16.00 μg/mL with a limit of detection (LOD) = 0.17 μg/mL. The nanoprobe achieved a high % recovery in assaying KETO in tablet dosage form and had not been significantly affected by various interferents including co-formulated and co-administered drugs. The nanoprobe shows selectivity toward KETO, even in the presence of its photocatalytic degradation products. It can effectively investigate the elimination of KETO from aquatic systems and test its stability in pharmaceutical preparations. The developed nanoprobe underwent a comprehensive evaluation of its environmental impact using analytical eco-scale (AES), complex green analytical procedure index (Complex GAPI), and the Analytical GREEnness calculator (AGREE). The sustainability of the developed nano sensor was assessed and compared to the reported metal-based quantum dots probe for KETO using the innovative RGB 12 model, considering 12 white analytical chemistry (WAC) perspectives.

Therapeutic drug monitoring of six contraindicated/co-administered drugs by simple and green RP-HPLC-PDA; application to spiked human plasma

Therapeutic drug monitoring is an important clinical testing of the drugs to monitor their concentrations in plasma in order to guarantee their optimal impact, and to avoid any side effects resulting from drug-drug interactions. A green reversed-phase high-performance liquid chromatographic method using a photodiode array detector (RP-HPLC-PDA) was developed for the simultaneous determination of three carbapenem antibiotics (Imipenem, ertapenem, and meropenem) with the co-formulated drug (cilastatin) and contraindicated drugs (probenecid and warfarin) in spiked human plasma. The separation was achieved at 25 °C using a gradient elution of a mixture of mobile phase A: methanol and mobile phase B: phosphate buffer (pH 3.0). The photodiode array detector was adjusted at 220 nm. Bioanalytical method validation was carried out as per the FDA guidelines, and the method showed good linearity ranges for the six drugs that included their Cmax levels along with low limits of quantification. Based on the results, the method was found to be accurate and precise; with high % recovery and good % RSD, respectively. The method was successfully applied to spiked human plasma, signifying a good potential to be implemented in future TDM studies of these drugs when co-administered together.

A highly sensitive micelle-enhanced synchronous spectrofluorimetric determination of the recently approved co-formulated drugs, bilastine and montelukast in pharmaceuticals and human plasma at nanogram levels.

In this study, the simultaneous determination of bilastine and montelukast, two recently approved co-formulated antihistaminic medications, was accomplished using a quick, sensitive, environmentally friendly, and reasonably priced synchronous fluorescence spectroscopic approach for the first time. Enhancement of the method's sensitivity down to nanogram levels was achieved by the addition of sodium dodecyl sulfate (1.0% w/v) as a micellar system. According to the results, bilastine and montelukast's fluorescence was measured at 255.3 and 355.3nm, respectively, using Δλ of 40.0nm and distilled water as a green diluting solvent. With respect to the concentration ranges of bilastine (5.0-300.0ng/ml) and montelukast (50.0-1000.0ng/ml), the method showed excellent linearity (r ≥ 0.9998). The results showed that the suggested method is highly sensitive, with detection limits of 1.42 and 13.74 ng/ml for bilastine and montelukast, respectively. Within-run precisions (intra- and interday) per cent relative standard deviations (RSD) for both analytes were <0.59%. With high percentage recoveries and low percentage RSD values, the designed approach was successfully applied for the simultaneous estimation of the cited medications in their dosage form and human plasma samples. To evaluate the green profile of the suggested method, an analytical GREENNESS metric approach (AGREE) and green analytical procedure index (GAPI) metric tools were used. These two methods for evaluating greenness confirmed that the developed method met the highest number of green requirements, recommending its use as a green substitute for the routine analysis of the studied drugs. The proposed approach was validated according to ICHQ2 (R1) guidelines.

Cobalt oxide nanoparticles modified coated graphite potentiometric sensor for quantification of sulfacetamide sodium in its pharmaceutical dosage form and spiked rabbit aqueous humor samples with greenness assessment

This study presents the fabrication of an innovative coated graphite electrode modified with cobalt oxide nanoparticles, for potentiometric determination of Sulfacetamide sodium. The functionalized nano-electrode was compared to a classical one; to study the advantages of addition of nanoparticles which was found to improve the performance characteristics of the electrode including improved sensitivity and selectivity, as well as, extended operational lifespan. The functionalized nano-electrode was more sensitive than the classical one with linearity range (1 × 10−7–1 × 10−2 M) and a limit of detection down to 2.24 × 10−8 M. This small modification increased the electrode’s potential stability by preventing the formation of a water layer on the surface of the solid contact electrode. The electrochemical performance of the proposed sensors was evaluated according to the IUPAC recommendation data and was found to be within the acceptable ranges. These developed potentiometric platforms were applied to quantitatively analyze Sulfacetamide sodium in its pure solutions, pharmaceutical dosage form and spiked rabbit aqueous humor with satisfactory recovery percentages without pre-extraction procedure nor interference of the co-formulated drug; Prednisolone acetate and excipients. The proposed method was statistically compared with the reported method in literature and no statistically significant difference was found. The proposed method was evaluated for its environmental sustainability utilizing the Green Analytical Procedure index (GAPI) as a greenness assessment tool.

Electrochemically-selective electrode for quantification of dorzolamide in bulk drug substance and dosage form

Three smart carbon paste electrodes were fabricated to quantify dorzolamide hydrochloride DRZ, including conventional carbon paste I, modified carbon paste embedding Silica II, and modified carbon paste embedding β-cyclodextrin III. This study is based on the insertion of DRZ with phosphomolybdic acid to create an electroactive moiety dorzolamide-phosphomolybdate ion exchanger using a solvent mediator dibutyl phthalate. The three constructed carbon paste electrodes displayed Nernstian responses and linear concentration ranges with lower detection limits. The vital performance of the created electrodes was verified in relation to various parameters. The electrodes enhance the selective determination of DRZ in the presence of inorganic ions, a co-formulated drug in the dosage form timolol maleate, and the excipient benzalkonium chloride. The modified carbon paste electrode including Silica was utilized to detect DRZ in ophthalmic eye drop form utilizing the direct calibration curve and potentiometric titration methods. Satisfactory findings were achieved by comparing them to other reported methods.

Sustainable eco-friendly ratio-based spectrophotometric and HPTLC-densitometric methods for simultaneous analysis of co-formulated anti-migraine drugs with overlapped spectra

Considering the green chemistry perspective and improving the environmental impact of quality control labs; two direct techniques with less hazardous solvents, less waste production and less energy consumption were developed for simultaneous analysis of Aspirin and Metoclopramide in bulk powder and pharmaceutical formulation. The ratio between the two drugs in their co-formulated preparation is very challenging; (90: 1, Aspirin: Metoclopramide). The first technique is spectrophotometry using simple mathematical operations; ratio difference and derivative ratio–zero crossing. The second technique is high-performance thin-layer chromatography (HPTLC) -densitometry which used a mobile phase consisting of cyclo-hexane: methanol: methylene chloride in a ratio of (1:4:1, v/v/v). The greenest solvents which give acceptable resolution were chosen. Following the International Conference on Harmonization (ICH) guidelines, the methods were found to be accurate, precise, and selective. Those methods were statistically compared to the reported spectrophotometric method and the results proved that there is no significant difference in accuracy and precision. Furthermore, the developed methods were assessed using the Analytical Eco-scale, Green Analytical Procedure Index (GAPI) and the Analytical Greenness calculator (AGREE), which gave a full image about their greenness profile. The spectrophotometry was found to be an excellent green technique compared to HPTLC with was considered an acceptable green one. The developed HPTLC-densitometric method was used for the first time for the analysis of this binary mixture. The two proposed spectrophotometric methos have advantages over the published methods as they used easy manipulation steps and are applied on the market pharmaceutical formulation. Owing to the advantages of the developed techniques; being green, do not require expensive sophisticated equipment or large volume of solvents; they could be used for routine analysis in quality control aspects.

Hydro-organic mobile phase and factorial design application to attain green HPLC method for simultaneous assay of paracetamol and dantrolene sodium in combined capsules

The greenness of any analytical method has become a very important aspect of a good analytical method. However, most chromatographic methods depend on the usage of relatively large amounts of lethal and un-decaying chemicals and solvents. So, a green approach based on the full factorial design was employed to develop a simple and rapid HPLC technique for concurrent determination of paracetamol and dantrolene sodium in their combined capsules. Both drugs are highly recommended to be administered together in patients with severe musculoskeletal disorders. Avoiding the routine methodology and resorting to the modern technology represented in the usage of experimental design allows rapid determination of the studied drugs using the optimum quantity of chemicals to avoid any waste of resources. Simultaneous separation of a binary mixture of paracetamol and dantrolene sodium was accomplished using a reversed phase Hypersil C18 column using an eco-friendly isocratic eluent. The used mobile phase consisted simply of ethanol: water (40:60, v/v). Orthophosphoric acid was used to adjust the pH of the mobile phase to 4.5. Triethanolamine (0.2%) was added aiming to reduce the peak tailing. The assay was completed within less than 6 min adopting 0.8 mL/min as a flow rate. The detection was carried out using a UV-detector at 290 nm. The suggested technique shows a linear correlation over concentration ranges of 1.0–200 and 1.0–40 µg/mL for paracetamol and dantrolene sodium, respectively. The suggested technique allowed the simultaneous analysis of the two co-formulated drugs in their synthetic mixture and combined capsule. The suggested technique is considered a greener substitute for the other reported HPLC techniques through the usage of safer solvents and chemicals, along with decreasing both waste output and analysis time. The method is accurate with recoveries between 97.85 and 101.27%, precise, as %RSD for the intraday and interday precision were between 0.39 and 1.72% and very sensitive with limits of detection (LOD)’s 0.15 and 0.18 µg/ml and limits of quantification (LOQ)’s 0.48 and 0.61 µg/ml for paracetamol and dantrolene sodium, respectively. The method greenness was ensured through its assessment by four greenness metrics. It is also validated following the International Conference on Harmonization Guidelines. The recommended technique could be a good alternative to traditional methods in the routine quality control analysis of the studied drugs due to its minimum harm to the planet or human beings.

Integrating micellar HPLC and green analytical chemistry tools in greenness assessment of five commonly Co-formulated antidiabetic drugs

The ecological impact of routine quality control activities in the pharmaceutical industry is crucial, producing large amounts of dangerous organic waste. For that, the use of mixed-micellar LC was found beneficial. When sodium dodecyl sulfate (SDS) is mixed with Brij-35 as surfactants in the mobile phase, no organic modifier was needed for enhancing the analytes' elution time or resolution. In the proposed study, five antidiabetic drugs belonging to different antidiabetic classes; namely metformin (MTF), glibenclamide (GBC), gliclazide (GCZ), linagliptin (LNT) and dapagliflozin (DPF), have been studied using organic-solvent free Micellar RP-HPLC technique. The combination of double or even triple antidiabetic therapies from different classes is common and was proved efficient for the control of type-2 diabetes. The optimal mobile phase was composed of 0.12 M SDS, 0.008 M Brij-35 and 0.15 M triethylamine in water, adjusted to pH 4.5. The flow rate was set at 1.5 mL min−1 on RP-monolithic column (100 × 4.6 mm). Photodiode array detection was set at wavelength 245 nm for MTF and 225 nm the other analytes. Linearity ranges were 50–600 μg mL−1 for MTF, and 5–60, 2.5–30, 7.5–60, and 2.5–30 μg mL−1 for DPF, LNT, GCZ and GBC, respectively (R2 ≥ 0.997). Trueness and precision have been established across the specified ranges with recovery percentages range 98–105% and relative standard deviation of the results less than 2.5%. The obtained results of resolution, peaks’ symmetry and theoretical plates for the drugs under study proved the analytical capability of using mixed-micellar mobile phases for elimination of the organic-solvents without affecting the separation efficiency.

Application of Principal Component Analysis and DoE-Driven Green Analytical Chemistry Concept to Liquid Chromatographic Method for Estimation of Co-formulated Anti-Hypertensive Drugs.

The fixed-dose combination (FDC) of metoprolol succinate (MTS), cilnidipine (CDN), and telmisartan (TST) is used for the management of hypertension. Numerous reversed phase (RP)-HPLC methods have been reported in the literature for chromatographic analysis of MTS, CDN, and TST. According to the concept of green analytical chemistry (GAC), toxic organic solvents should be avoided or minimized during chromatographic method development for the safety of analysts and the protection of the environment. The reported RP-HPLC methods have been developed using acetonitrile (ACN) or methanol as an organic component of the mobile phase and diluent for sample preparation. These organic solvents are considered toxic solvents as per the International Council for Harmonization (ICH) Q3C (R6) guideline and Pfizer medicinal chemistry solvent selection (PMCSS) guide. We aimed to develop an environment-friendly and economical RP-HPLC-photo-diode array (PDA) method for the analysis of MTS, CDN, and TST using less toxic organic solvents to support the concept of GAC. The method development was carried out by the implementation of chemometrics and design of experiments (DoE) to avoid wastage of organic solvent. Principal component analysis (PCA) was applied as a chemometric tool for the identification of critical method risk variables (MRVs) and method performance attributes (MPAs). The identified critical MRVs and MPAs were further studied by DoE-based response surface modelling for optimization of the method. The chromatographic analysis of MTS, CDN, and TST was carried out using a Shim-pack ODS column as a stationary phase and ethanol as an organic modifier in the mobile phase. The developed method was applied to the assay of FDCs and results were found to be in compliance with the label claim. The greenness profiles of reported and present RP-HPLC methods were evaluated by national environmental method index (NEMI) and analytical greenness (AGREE) methods. The developed method was found to be green, robust, and economical as compared to published methods for the analysis. Development and validation of an RP-HPLC method for simultaneous estimation of MTS, CDN, and TST using safe organic solvents. Implementation of a analytical quality by design (AQbD) approach in method development using PCA and DoE. Application of the method for assay of FDCs of MTS, CDN, and TST.

An eco-friendly HPLC method for concurrent determination of carbocisteine, guaifenesin, and oxomemazine in their combined formulations

The respiratory tract infections have a growing concern by healthcare specialists. Carbocisteine, guaifenesin, and oxomemazine are widely used as co-formulated anti-cough drugs. For the first time, a precise, accurate, and green HPLC method has been developed and validated for their determination in their combined dosage forms. The separation was accomplished using a photodiode array detector at 220 nm with an isocratic green mobile phase consisting of phosphate buffer 0.025 M, (pH 3) and ethanol (75:25, v/v) at a flow rate of 1.0 mL/min and ambient temperature. The developed method was validated in accordance with ICH guidelines. Carbocisteine, guaifenesin, and oxomemazine were separated in less than 12 min at 1.569 ± 0.005 min, 8.546 ± 0.007 min, and 10.877 ± 0.008 min, respectively. The linear ranges for carbocisteine, guaifenesin, and oxomemazine were 31.25–187.50, 25–150, and 0.5–3.0 µg/mL, respectively. The developed method can be used in quality control laboratories for the simultaneous determination of the investigated drugs in their pharmaceutical dosage forms. In addition, it proved its superiority over the reported methods in terms of greenness using different assessment tools.

Development of Sٍٍensitive Spectrofluorimetric Methods for Determining Netilmicin Based on Selective Condensation Reactions of its Amine Moiety with each Acetylacetone/Formaldehyde and Ninhydrin/Phenylacetaldehyde Reagents

Netilmicin is an aminoglycoside antibiotic used to treat infections caused by a broad spectrum of Gram-negative and Gram-positive bacteria and is pharmaceutically formulated in ophthalmic dosage forms. In this study, two spectrofluorimetric approaches were designed and developed to switch-on the fluorescence activity of NTC. The first method, or Hantzsch (HNZ) method, was relied on measuring the generated fluorescence intensity upon the condensation of NTC with acetylacetone and formaldehyde (Hantzsch reaction) at λemis=483 nm/λexcit=425.5 nm. While the second fluorometric method (NHD method) was relied on measuring the generated fluorescence intensity upon the condensation of NTC with ninhydrin/phenylacetaldehyde at λemis=482.2 nm/λexcit=385.8 nm. The reaction conditions for the two approaches were well investigated and optimized. The selectivity study for the methods was investigated by determining NTC in the presence of the co-formulated drug (dexamethasone) and pharmaceutical excipients. The validation for two approaches was performed based on ICH guidelines, and ranges of linearity were 0.1-1.2 and 1.5-6.0 µg/mL, while LOD values were 0.039 and 0.207 µg/mL for the HNZ method and the NHD method, respectively. Finally, NTC has been determined in different ophthalmic preparations by the proposed approaches with adequate recovery values.

Green quality by design HPLC approach for the simultaneous determination of Bilastine and Montelukast

For the simultaneous estimation of two co-formulated antihistaminic drugs (Bilastine and Montelukast), a novel and eco-friendly reversed-phase HPLC approach with both diode array and fluorescence detection modes was designed. Rather than using the routine methodology, the Quality by Design (QbD) approach was adopted to speed up the method development and to test robustness of the method. To evaluate the effect of variable factors on chromatographic response, a full factorial design was used. The chromatographic separation was performed using isocratic elution on the C18 column. The mobile phase consists of 92% methanol, 6% acetonitrile, and 2% phosphate buffer with 0.1 (v/v) triethylamine adjusted to pH 3, it was pumped at a flow rate of 0.8 mL/min with an injection volume of 20 μL. The developed stability indicating HPLC approach was used to assess the stability of montelukast (MNT). It was subjected to a variety of stress conditions, including hydrolytic (acid–base), oxidative, thermal, and photolytic stress conditions. All of these conditions were found to have relevant degradation pathways. Under the described experimental conditions, MNT degradation followed pseudo-first-order kinetics. The kinetic parameters of its degradation (rate constant and t1/2) were calculated and a proposal for the degradation pathway was postulated.

Novel fabricated potentiometric sensors for selective determination of carbinoxamine with different greenness evaluation perspectives

Electrochemical sensors, such as ion-selective electrodes (ISEs) is one of the promising green analytical techniques with significant advances that opens up new frontiers of its application. In this contribution, we developed and validated novel potentiometric sensing method for selective monitoring of carbinoxamine maleate (CRX) in presence of the co-formulated drugs. A comparative potentiometric study was employed using a dual design of ISEs; a classical liquid inner-contact and solid-contact sensors. Herein, a full investigation of the opportunities and challenges offered by the two ISEs assemblies and configurations were discussed. Taking into consideration the impressive added values of solid-contact ISEsover the conventional ones, including: being eco-friendly, real-time analyzers, portable, disposal, maintenance-free, easily miniaturized, and compatible with microfabrication technologies. The backbone of the solid contact electrode is the incorporation of ionophore (2-hydroxypropyl-β-cyclodextrin) as supramolecular element and a network of multi-walled carbon nanotubes as ion-to-electron transducer in a single-piece nanocomposite membrane. Besides, the fabrication of solid-state ISEs was performed via simple one-step drop casting of the ion sensing mixture on surface of microfabricated electrode.Furthermore, the morphological and structural features of the obtained membrane were characterized using Raman spectroscopy and scanning electron microscopy (SEM) techniques. The suggested sensors were successfully applied for quantitation of CRX in its pure and dosage form. Performances of fabricated sensors were assessed as per IUPAC recommendations. The outcomes of the proposed method were statistically benchmarked to the official approach, where no significant difference was found. Moreover, a comprehensive greenness evaluation of the investigated method was performed via various green-metrics, namely, GAM, Eco-Scale, GAPI and AGREE algorithm which is utilized 12 principles of green analytical chemistry. Finally, studying the whiteness degree of the established method was conducted using the recently introduced RGB12 model.

Screen-printed sensors for efficient potentiometric analysis of tolperisone hydrochloride in presence of its co-formulated drugs

Researchers seeking for green chemistry to help safeguard and boost the economy and the environment by discovering unique ways to decrease waste and find substitutes for dangerous chemicals. In this study, a green potentiometric ion-selective electrode (ISE) was developed for measurement of tolperisone HCl (TOLP) in bulk and Pharmaceutical dosage forms in presence of diclofenac sodium and paracetamol as co-formulated drugs. This paper presents the manufacture and characterization of a disposable potentiometric ion-selective strip with an enhanced detection limit for (TOLP) measurement in its tablet dosage form either alone or in presence of the co-formulated drugs. Numerous ion pairs (IPs), such as TOLP-tetraphenylborate (TOLP-TPB), TOLP-phosphotungstic acid (TOLP-PTA), and TOLP-ammonium Reinecke (TOLP- RKT) are tested in presence of different plasticizers. The optimal potentiometric response with a near Nernstian slope of 55.949 mV/decade was achieved within a linear concentration range of 5 times 10–5 − 1 times 10–2 M using (PTA) and ortho nitrophenyl octyl ether (o-NPOE) as a plasticizer. The effect of the nanoparticles on the membrane stability was studied using the graphene nanoplatelets which have an effective role in the enhancement of some constructed sensors stability. Finally, the developed technique is validated for the estimation of TOLP with high accuracy and precision.Graphical

Fluorescent carbon dots as selective nano probe for determination of diacerein in presence of co-formulated drugs

In this work, a new and simple carbon dots (CDs) based fluorescent probe was introduced for selective determination of diacerein (DIA) in presence of two co-formulated drugs. This highly fluorescent sensor was constructed using chitosan as a carbon and nitrogen source by single step carbonization. The constructed probe is based on the inner filter effect (IFE), in which DIA serves as a strong absorber, influencing the excitation of the fluorescer (CDs). This overlap leads to quenching of CDs fluorescence upon increasing DIA concentration within the range of 2.5–17.5 µg/mL with mean % recovery reached to 99.7 ± 0.7. The performance of the constructed sensor had been validated according to the ICH guidelines and the results revealed that it is precise and accurate. Moreover, it has many advantages such as simplicity, saving time and good selectivity for the determination of DIA as a minor component in presence of co-formulated drugs in its tablet dosage form.

Multifunctional Lipid Bilayer Nanocarriers for Cancer Immunotherapy in Heterogeneous Tumor Microenvironments, Combining Immunogenic Cell Death Stimuli with Immune Modulatory Drugs.

In addition to the contribution of cancer cells, the solid tumor microenvironment (TME) has a critical role in determining tumor expansion, antitumor immunity, and the response to immunotherapy. Understanding the details of the complex interplay between cancer cells and components of the TME provides an unprecedented opportunity to explore combination therapy for intervening in the immune landscape to improve immunotherapy outcome. One approach is the introduction of multifunctional nanocarriers, capable of delivering drug combinations that provide immunogenic stimuli for improvement of tumor antigen presentation, contemporaneous with the delivery of coformulated drug or synthetic molecules that provide immune danger signals or interfere in immune-escape, immune-suppressive, and T-cell exclusion pathways. This forward-looking review will discuss the use of lipid-bilayer-encapsulated liposomes and mesoporous silica nanoparticles for combination immunotherapy of the heterogeneous immune landscapes in pancreatic ductal adenocarcinoma and triple-negative breast cancer. We describe how the combination of remote drug loading and lipid bilayer encapsulation is used for the synthesis of synergistic drug combinations that induce immunogenic cell death, interfere in the PD-1/PD-L1 axis, inhibit the indoleamine-pyrrole 2,3-dioxygenase (IDO-1) immune metabolic pathway, restore spatial access to activated T-cells to the cancer site, or reduce the impact of immunosuppressive stromal components. We show how an integration of current knowledge and future discovery can be used for a rational approach to nanoenabled cancer immunotherapy.

Smart spectrophotometric methods for stability assessment of two co-formulated antigout drugs

Simple, sensitive and accurate stability indicating spectrophotometric methods have been developed for the simultaneous determination of probenecid, colchicine as well as colchicine degradation product in their ternary mixture. Probenecid was firstly assayed using the double divisor ratio spectra derivative method. On the other hand, three spectrophotometric methods, namely: ratio difference, derivative ratio and mean centering of ratio spectra, have been suggested for the simultaneous quantification of colchicine and its degradation product. The obtained calibration curves were linear at 2.5–30.0 μg/mL, 0.5–25.0 μg/mL and 1.0–13.0 μg/mL for probenecid, colchicine and colchicine degradation product, respectively. The investigated methods were validated in accordance with the International Council for Harmonisation guidelines and were effectively used for quantification of probenecid and colchicine in their bulk powders and combined pharmaceutical dosage form.