Combined Pharmaceutical Formulation Research Articles

Smartphone based TLC approach versus conventional densitometric measurement for the simultaneous determination of donepezil and memantine, content uniformity testing along with greenness and whiteness assessment

Thin layer chromatography (TLC) is a straightforward and economical technique that plays a major role in analytical field. Introducing the amenities of smartphones as accessible alternative detectors to TLC separation methods elaborates the cost-effectiveness of this technique and supports the appropriate assay of various aliphatic compounds after visualization by suitable reagents. Herein, two TLC coupled with smartphone's camera approaches are proposed for the assay of donepezil hydrochloride (DON) and memantine hydrochloride (MEM), a combined medication used in the management of Alzheimer's disease. Separation was achieved using a developing system of ethyl acetate, methanol, toluene, and ammonia (33%, w/v) in a ratio of 4:1:4:0.2, by volume. The dried plates were scanned at 190 nm for the densitometric assay, then visualized with modified Dragendorff's reagent and photographed by smartphone's camera. The data were integrated by displaying the photos in either ImageJ software or Color-Picker application. The findings produced from the three detection approaches were contrasted over concentration ranges of 1–18 & 4–28 μg/spot for the densitometric method, while the range was 1–20 & 1–30 μg/spot for the ImageJ method and 3–18 & 2–20 μg/spot for the Color-Picker method for DON and MEM, respectively. The methods were suitable for assaying both drugs in their pure form and combined pharmaceutical formulations. Densitometric and ImageJ-based methods were applied to evaluate the dosage forms content uniformity. The developed methods were assessed by three metric tools for greenness and sustainability, namely Green Analytical Procedure Index, Analytical GREEnness Metric Approach, and White Analytical Chemistry.

Green micellar factorial design optimized first derivative synchronous spectrofluorimetric method for tripelennamine and diphenhydramine determination in pharmaceutical gel.

A green micellar synchronous spectrofluorimetric method was developed and validated for simultaneous determination of tripelennamine hydrochloride and diphenhydramine in bulk and combined pharmaceutical formulation. Synchronous fluorescence of tripelennamine hydrochloride and diphenhydramine was determined using Δλ = 60 nm. The first derivative of synchronous fluorescence was computed to resolve overlap in the synchronous fluorescence spectra. Tripelennamine hydrochloride was quantified at 375 nm, whereas diphenhydramine was quantified at 293 nm; each is the zero-crossing point of the other. As diphenhydramine exhibited weak native fluorescence, micelle enhancement upon incorporation of sodium dodecyl sulfate was considered. Two-level full factorial design was carried out to optimize experimental parameters. Optimum conditions involved using SDS (2% w/v) along with Teorell and Stenhagen buffer (pH9). The method was found to be linear over the range 0.2-4.5 and 0.2-5μg/mL for tripelennamine and diphenhydramine, respectively, with limits of detection 0.211 and 0.159 μg/mL. The method was successfully applied for simultaneous determination of tripelennamine hydrochloride and diphenhydramine in laboratory-prepared gel containing all possible excipients with mean percent recoveries ±SD 100.59 ±0.79 and 98.99 ±0.98 for tripelennamine hydrochloride and diphenhydramine, respectively. The proposed method was proved to be eco-friendly using different greenness assessment tools.

Application of smart chemometric models for spectra resolution and determination of challenging multi-action quaternary mixture: statistical comparison with greenness assessment

A multivariate spectrophotometric method is a potential approach that enables discrimination of spectra of components in complex matrices (e.g., pharmaceutical formulation) serving as a substitution method for chromatography. Four green smart multivariate spectrophotometric models were proposed and validated, including principal component regression (PCR), partial least-squares (PLS), multivariate curve resolution-alternating least squares (MCR-ALS), and artificial neural networks (ANN). The developed chemometric models were compared to resolve highly overlapping spectra of Paracetamol (PARA), Chlorpheniramine maleate (CPM), Caffeine (CAF), and Ascorbic acid (ASC). The four multivariate calibration models were assessed via recoveries percent, and root mean square error of prediction. Hence, the proposed models were efficiently applied with no need for any preliminary separation step. The models were utilized to analyze the studied components in their combined pharmaceutical formulation (Grippostad® C capsules). Analytical GREEnness Metric Approach (AGREE) and eco-scale tools were applied to assess the greenness of the established models and found to be 0.77 and 85, respectively. Moreover, the proposed models have been compared to official ones showing no considerable variations in accuracy and precision. Therefore, these models can be highly advantageous for conducting standard pharmaceutical analysis of the substances researched within product testing laboratories.

Two green and sensitive spectrofluorimetric approaches for determination of Ambroxol and guaifenesin in their single and combined pharmaceutical formulations.

Ambroxol hydrochloride (AMX) and guaifenesin (GFN) are approved drugs utilized to treat coughs through their potent mucolytic and expectorant properties. Due to their massive, combined administration in many illnesses, there is a persistent need for their concurrent estimation in different pharmaceutical formulations. Two sensitive, environmentally friendly spectrofluorimetric methods were developed. AMX was determined using the first method (I) without interference from GFN. This method depends on the quenching of Erythrosine B (EB) native fluorescence at 552 nm after excitation at 527 nm due to the formation of a non-fluorescent AMX-EB ion-pair complex in Britton-Robinson buffer (BRB) solution pH (3.5). The concentration plot is linear over the 0.25-5.0μg/mL range, with a mean percent found value of 99.74%. Method (II) depends on measuring the native fluorescence of aqueous GFN solution at two analytical wavelengths, either 300 or 600 nm, after excitation at 274 nm. Relative fluorescence intensity (RFI)-concentration plots are linear over the ranges of 0.02-0.5 and 0.1-2.0μg/ml, with mean percent found at 99.96% and 99.91% at dual wavelengths, respectively. The proposed methods were successfully applied to assay both drugs in raw materials and different single and combined pharmaceutical formulations. These methods have been thoroughly validated following International Committee on Harmonisation (ICH) guidelines. National Environmental Methods Index, Analytical Eco-Scale, and Green Analytical Procedure Index were used to prove greenness, thereby enhancing their applicability. The proposed techniques provide straightforward, precise, and cost-effective solutions for routine formulation analysis in quality control laboratories.

Development of chromatographic methods to determine multivitamins formulation depending on their solubility and polarity: comparative study using three greenness assessment tools

High performance liquid chromatography is one of the techniques of choice for the separation and quantitative determination of drugs in mixture form. Ipriflavone, ascorbic acid, pyridoxine, vitamin D3, and lysine are formulated together as an adjuvant combination in osteoporosis. In this work, we developed and validated two complementary high performance liquid chromatographic methods to determine the five compounds in their pharmaceutical dosage form. The first method (method A) was capable of determining ipriflavone, ascorbic acid, pyridoxine, and vitamin D3 in their bulk and combined pharmaceutical formulation. The method is based on Liquid Chromatographic separation with UV detection at 254 nm using Agilent Eclipse XDB-C18 column with a mobile phase consisting of 25 mM ammonium acetate buffer (pH 4.2): methanol in gradient mode. Due to the high polarity of lysine, it was difficult to achieve satisfactory retention on reversed phase columns. So, we separated it on a strong cation exchange column (Exsil 100 SCX) without derivatization with a mobile phase consisting of 10 mM sodium dihydrogen phosphate and 200 mM sodium chloride (pH 6) with UV detection at 210 nm (method B). Validation of the proposed methods was performed according to ICH guidelines Q2(R1). The proposed methods proved to be valid for selective analysis of the stated drugs in their bulk and combined pharmaceutical formulation. Greenness assessment of the developed methods was evaluated using three assessment tools: ESA, GAPI and the most recently developed tool AGREE, showing a satisfactory comprehensive guide of the greenness of the developed methods.

The application of experimental design and green analytical chemistry in HPLC strategy for the determination of five drugs used in antimicrobial combination therapy

Antimicrobial resistance is a significant global issue that has increased mortality rates over the past 100 years. One of the strategies followed to overcome this problem is to use antimicrobial combination therapy with different action modes that can synergize for successful treatment in emergent situations. Ciprofloxacin, Tinidazole, Dexamethasone Sodium Phosphate, Diloxanide Furoate, Metronidazole, and their different combinations are commonly used as effective combination therapies in critical cases. Hence, it is essential to establish an appropriate technique for their simultaneous analysis. The application of green analytical chemistry concepts was also an important issue that should be considered in the development of analytical methods. Hence, a new green micellar organic solvent-free HPLC methodology has been devised to analyze the specified five drugs simultaneously in both their authentic forms and combined pharmaceutical formulations. Response surface methodology was used to investigate the influence of different variable factors on chromatographic performance. Central composite design was utilized for response optimization. A Symmetry C18 column (3.5 µm, 4.6 × 75 mm), an isocratic mixed–micellar mobile phase composed of (70.76 mM of sodium dodecyl sulphate and 21.38 mM of Brij-35, 2.76 pH, and 40 ± 2 °C at a flow rate of 1 mL/min, were the ideal separation circumstances for analytesʹ separation at 260 nm as a chosen detection wavelength. The described approach was satisfactorily utilized todetermine various pharmaceutical formulations of the specified medications in combination. ICH guidelines were followed during the method's validation. Analytical Greenness Measure (AGREE) and Green Analytical Procedure Index (GAPI) fundamentals were followed to judge the developed methodology's greenness.

Stability-indicating HPLC-DAD and TLC-densitometry methods for the quantification of bupivacaine and meloxicam in their co-formulated mixture

The implementation of a novel drug formulation necessitates the assessment of its content stability and the designation of appropriate stability monitoring methodologies. Bupivacaine (BVC) and Meloxicam (MLX) were recently authorized under the name Zynrelef® solution. This novel combination was tested for stability under a variety of stress circumstances for the first time in this study. The basic degradation pathway was shown to affect BVC, while the acidic degradation pathway works for MLX. Identification of the acquired degradation products, including BVC impurity F (BVC IMP-F), 1-buytylpiperidine-2- 2carboxylic acid (1-BPC), MLX acid degradation product (MLX-DEG), and MLX impurity B (MLX IMP-B), was carried out using IR and MS spectroscopic techniques. HPTLC and HPLC, two chromatographic-based stability-indicating methods, have been established. The HPTLC method offered efficient separation upon the usage of silica gel 60 F254 as a stationary phase and ethyl acetate/toluene/triethylamine/acetic acid (4:4:2:0.4, v/v/v/v) as a developing system with densitometric recording at 260 nm. The HPLC method was developed by using Zorbax® SB C18 column as a stationary phase and a mobile phase consisting of acetonitrile: methanol: phosphate buffer, pH 6.5 (20:60:20 v/v/v), at a flow rate of 1.5 mL min-1. Quantification of the analytes was performed at 265 nm using a diode array detector. The current research introduced the first stability-indicating methods for the assay of BVC and MLX which were successfully applied for the determination of the cited drugs in their combined pharmaceutical formulation. Moreover, the HPLC method was further extended for studying the degradation kinetics of the two drugs.

HPTLC- Densitometric method for assay of chlorthalidone, metoprolol succinate and telmisartan in combined pharmaceutical formulation

HPTLC- Densitometric method for assay of chlorthalidone, metoprolol succinate and telmisartan in combined pharmaceutical formulation

Eco friendly stability indicating HPTLC method for simultaneous determination of sofosbuvir and ledipasvir in pharmaceutical tablets and HPTLC-MS characterization of their degradation products

Recently, the analytical community has shown increasing interest in developing more environment-friendly practices by eliminating or reducing the use of hazardous chemicals and solvents which are extremely dangerous to human health and the environment. Thus in this study, a simple, rapid, inexpensive and eco-friendly HPTLC method with densitometric detection was designed, optimized and validated for the simultaneous quantitation of the antiviral drugs sofosbuvir (SOF) and ledipasvir (LED) in pure powder, synthetic mixtures, combined pharmaceutical formulation and in the presence of their stressed degradation products with high sensitivity and no interference. The separation was carried out on silica gel F254 plates, using green mobile phase ethyl acetate: water: ethanol (94:5:1v/v/v) for development followed by densitometric detection of SOF and LED at 250 and 320 nm, respectively. Both drugs had second order polynomial calibration curves within ranges 100–5000 ng/spot and 100–3000 ng/spot for SOF and LED, respectively, with correlation coefficients >0.9998 and the limits of detection were 30 and 29 ng/spot and the limits of quantification were 90 and 88 ng/spot for SOF and LED, respectively. The method was validated in terms of linearity, accuracy, precision, selectivity, and robustness. The drugs were subjected to acidic and basic hydrolysis, oxidation and photolytic conditions as per ICH guidelines, followed by detection of the degradation products and structure elucidation of their fragments with the aid of the HPTLC-ESI- MS technique. The greenness of the proposed method was assessed using the analytical Eco-Scale as an assessment tool with a 93-point score. So, it is considered excellent green.

A Review on Analytical Method Development for the Estimation of a Potent Muscarinic Receptor Antagonist Tolterodine Tartrate

Background: A pharmaceutical will be clinically accepted if it is impurity-free and its dose is accurately maintained. For this, the contribution of analytical techniques for developing and validating a new pharmaceutical dosage form cannot be overlooked. Introduction: Tolterodine tartrate is a potent competitive muscarinic receptor antagonist. It binds to the muscarinic M3 receptors in the bladder selectively and competitively. It is used to treat urinary incontinence and overactive bladder syndrome. The 5-hydroxymethyl derivative is the pharmacologically active metabolite of Tolterodine tartrate, which is as potent as the main drug. It is available with α-adrenergic blocker Tamsulosin in combined pharmaceutical formulations, treating benign prostatic hyperplasia in men. This review article presents several analytical methods, including HPLC, HPTLC, UV-Visible spectrophotometry, spectrofluorimetry, electroanalytical, and various hyphenated techniques like GC-MS, LC-MS, LC-MS-MS, etc., for estimation of Tolterodine tartrate is present as a single material or in combined form in bulk materials, different pharmaceutical formulations, and biological matrices. Conclusion: HPLC and spectrophotometry are the most widely used methods for determining the drug in the bulk and pharmaceutical dosage form among all these methods. LC-MS and LC-MSMS are widely used for the estimation of Tolterodine tartrate from plasma and other biological fluids. All the methods included in this article are accurate, sensitive, and cost-effective.

Novel microfabricated solid-contact potentiometric sensors doped with multiwall carbon-nanotubes for simultaneous determination of bisoprolol and perindopril in spiked human plasma

The main concern when developing solid contact ion selective electrodes is the choice of ion sensing membranes while keeping in mind, cost effectiveness, simplicity, potential stability, and reproducibility of results. The main aim of this work is to design microfabricated solid contact ion selective electrodes (SC-ISEs) for the selective determination of bisoprolol (BIS) and perindopril (PER) either in their combined pharmaceutical formulation or simultaneously in human plasma. The obstacle was improving the detection limit of the proposed microfabricated sensors so they can determine the plasma peak concentrations of both drugs. Two factors were considered, namely the addition of ionophores and doping the ion sensing membranes with multiwalled carbon nanotubes (MWCNTs). Four sensors were developed for BIS while two other sensors were developed for PER, and their electrochemical performance was assessed. Selectivity of the sensors was determined in presence of some degradation products, impurities and metabolites of BIS and PER. Doping the ion sensing membranes with MWCNTs proved to interfere with the formation of water layer, resulting in more stable performance. Furthermore, addition of calix[6]arene (CX6) increased the sensitivity in case of BIS sensor. The optimum results for BIS were obtained with ion sensing membrane of potassium tetrakis(4-chlorophenyl)borate, CX6 and MWCNTs. Whereas an ion sensing membrane of tetradodecylammonium bromide and MWCNTs, showed best response in case of PER. The linearity range obtained in case of BIS was 8 × 10−9–1 × 10−2 M with an LOD of 1.74 × 10−9M. While for PER, the linearity range was 1 × 10−8–1 × 10−2 M with an LOD of 9.12 × 10−9 M.

Selective Spectrofluorimetric Protocol for Determination of Commonly Used Gram-negative Bactericidal Drug in Combined Pharmaceutical Dosage Forms and Human Plasma.

Gram-negative bacteria cause infections such as skin infection, meningitis, and pneumonia in human being. Gram-negative bacteria are highly resistant to most availaible bactericidal drugs. One of the most commonly used Gram-negative bactericidal drug is Polymyxin B sulfate (PMS). In addition, it is used in cases of highly resistant Gram-negative bacterial infections. The widespread of PMS necessitate the development of an exceedingly sensitive and selective fluorimetric assay for its determination in pure form, different pharmaceutical dosage forms, and human plasma. The presented method is used to determine PMS in their dosage form (vials) and combined pharmaceutical formulations (skin and eye ointments) with a high degree of accuracy and selectivity. The described procedure relies on the structure of a derivative of a high degree of fluorescence called dihydropyridine, via the condensation of the amino moiety of PMS with two equivalents of acetylacetone in the presence of formaldehyde and Teorell buffer (pH = 3). The fluorescent product was measured at 471nm (λex = 402nm). The linearity ranged from 100-3000 ng mL-1 of PMS with an excellent r2 of 0.9998. LOD and LOQ were 27.16ngmL-1 and 82.30ngmL-1, respectively. Owing to the developed method's high selectivity, it was successfully utilized for assay of PMS, in the ointment, in the presence of oxytetracycline as an active ingredient. Furthermore, the procedure applied for the estimation of parenteral PMS in human plasma with very good mean recovery 97.42 ± 1.46.

A new stability indicating RP-UPLC method for simultaneous estimation of Doravirine, Lamivudine and Tenofovir disoproxil fumarate in bulk and their combined pharmaceutical formulation

BackgroundTo establish a simple, sensitive, accurate, precise, efficient, economical RP-UPLC method for simultaneous estimation of Doravirine, Lamivudine and Tenofovir disoproxil fumarate in bulk and their combined pharmaceutical formulations. Optimization of Chromatographic separation was achieved on analytical column HSS C18 (100 × 2.1 mm, 1.8 μ) maintained at temperature 30 °C and mobile phase consisting of 0.01 N Potassium dihydrogen orthophosphate buffer (pH-4.8) and acetonitrile in the ratio 60:40 v/v and at a flow rate 0.3 mL/min in isocratic mode. The injection volume was set as 1 µl detection wavelength is 260 nm. The proposed method validation was done as per International Council on Harmonization Q2 (R1) guidelines.ResultsDoravirine, Lamivudine and Tenofovir disoproxil fumarate were eluted at retention times of 1.2, 1.5, and 1.8 min respectively. The proposed method was identified an excellent linearity over concentration range of 12.5–75.0 µg/mL for Doravirine and 37.5–225.0 µg/mL for Lamivudine and 37.5–225.0 µg/mL for Tenofovir disoproxil fumarate. The percentage relative standard deviation for intra-day and inter-day precision of the present method was less than 2% for Doravirine, Lamivudine and Tenofovir disoproxil fumarate. Accuracy of the present method was evaluated by recovery studies which were in the range of 99.62–99.88% for Doravirine and 98.78–99.44% for Lamivudine and 99.67–100.52% for Tenofovir disoproxil fumarate. The limit of detection and limit of quantification were found to be 0.249 µg/mL and 0.756 µg/mL for Doravirine and 0.24 µg/mL and 0.727 µg/mL for Lamivudine and 0.797 µg/mL and 2.966 µg/mL for Tenofovir disoproxil fumarate. Forced degradation studies were carried out under various stress conditions like acid, base, peroxide, thermal, photo and neutral conditions.ConclusionsThe present method makes sure about no degraded impurity peak interference at the retention time of analyte peak hence can be applied for quality control investigation of Doravirine, Lamivudine and Tenofovir disoproxil fumarate in bulk and pharmaceutical formulations.

A VALIDATED TLC- DENSITOMETRY FOR THE SIMULTANEOUS DETERMINATION OF TAMSULOSIN AND DUTASTERIDE IN THEIR COMBINED PHARMACEUTICAL FORMULATION.

A TLC densitometric method was developed and validated for simultaneous determination of dutasteride and tamsulosin in their challenging combined pharmaceutical formulation, where the separation process was achieved using a mobile phase composed of ethyl acetate: methanol: hexane: ammonia (90: 5: 3: 2 by volume) on pre-coated silica gel (60 GF254) plates, densitometric quantification was performed at 270 nm for both drugs. TAMS and DUTA were resolved with Rf values of 0.57± 0.01 and 0.72 ± 0.01 with a mean percentage recovery of 100.51 ± 0.659 and 100.81 ± 0.743, respectively. Method validation was performed following the International Conference on Harmonization (ICH) guidelines and was victoriously applied for simultaneous determination of tamsulosin HCl and dutasteride in their pharmaceutical formulation. The acquired results of the Proposed method were statistically compared with those acquired by the reported methods, demonstrating no significant difference. Therefore, the proposed method has the potential for being fast, simple, economic, and selective for sustainable analysis of the cited drugs.

Comparative Study for the Assay of Plant Derived Chemicals in Pharmaceutical Formulation Using Methods Dependent on Factorized Spectra.

Modern built-in spectrophotometer software supporting mathematical processes provided a solution for increasing selectivity for multicomponent mixtures. Simultaneous spectrophotometric determination of the three naturally occurring antioxidants-rutin(RUT), hesperidin(HES), and ascorbic acid(ASC)-in bulk forms and combined pharmaceutical formulation. This was achieved by factorized zero order method (FZM), factorized derivative method (FD1M), and factorized derivative ratio method (FDRM), coupled with spectrum subtraction(SS). Mathematical filtration techniques allowed each component to be obtained separately in either its zero, first, or derivative ratio form, allowing the resolution of spectra typical to the pure components present in Vitamin C Forte® tablets. The proposed methods were applied over a concentration range of 2-50, 2-30, and 10-100 µg/mL for RUT, HES, and ASC, respectively. Recent methods for the analysis of binary mixtures, FZM and FD1M, were successfully applied for the analysis of ternary mixtures and compared to the novel FDRM. All were revealed to be specific and sensitive with successful application on pharmaceutical formulations. Validation parameters were evaluated in accordance with the International Conference on Harmonization guidelines. Statistical results were satisfactory, revealing no significant difference regarding accuracy and precision. Factorized methods enabled the resolution of spectra identical to those of pure drugs present in mixtures. Overlapped spectra of ternary mixtures could be resolved by spectrum subtraction coupled FDRM (SS-FDRM) or by successive application of FZM and FD1M.

Analytical eco‐scale and quality by design‐oriented liquid chromatography method for simultaneous quantification of metoprolol succinate, telmisartan, and cilnidipine in their fixed‐dose combination

AbstractA new combination of metoprolol succinate, telmisartan, and cilnidipine is recently approved to treat hypertension effectively. A reversed‐phase liquid chromatography method was developed to quantify the said compounds, combining analytical eco‐scale and quality‐by‐design approach. The former one revealed an excellent green score for the present method. Later, method variables were assessed for risks and optimized using the quality‐by‐design‐oriented method development. The optimization process included using a Box‐Behnken design, and the obtained response surfaces for resolution amongst target peaks were mapped systematically. The optimal separation conditions employed a mobile phase of methanol: 0.01 M KH2PO4 buffer of pH 3.0 (70:30, %v/v) flowing at a rate of 1.0 mL/min on a C18 column with diode array detection at 240 nm. All three analyte peaks were well separated from each other with a resolution greater than 2.0. The analytical method was linear (2.5‐80 μg/mL) for target compounds with accuracy (>99%), and precision (<1%) results complying with regulatory requirements. The results of detection and quantitation limits, solution stability, and system suitability limit were good and acceptable. The current method selectively quantified the analytes from commercial dosage forms. Overall a green analytical method is developed and suitable for estimating metoprolol, telmisartan, and cilnidipine simultaneously in their combined pharmaceutical formulations.

Validated stability indicating RP-HPLC method for simultaneous determination of netupitant and palanosetron in combined pharmaceutical formulations

A simple stability indicating high performance liquid chromatographic method has been developed for the simultaneous determination of Netupitant and palanosetron using reverse phase Kromasil C18 (4.6 x 150mm, 5µm) with UV detector at 240nm. The mobile phase consisting of ACN, Potassium disodiumhydrogen phosphate in the ratio of 40:60 (v/v) and at a flow rate of 1 mL/min. The method was linear over the concentration range of 75-450μg/m for Netupitat and 0.125-0.75μg/m for palanosetron. The method was validated and was successfully employed for the routine quantitative analysis of pharmaceutical formulations containing Netupitant and Palanosetron in combined tablet dosage form.

Potentiometric sensing platform for selective determination and monitoring of codeine phosphate in presence of ibuprofen in pharmaceutical and biological matrices

Recently, application of ion selective electrode field in pharmaceutical sciences has expanded due to the most interesting feature of the sensors, which is their remarkably selective recognition. In this work six electrodes were investigated for codeine phosphate (COD) determination including conventional liquid inner contact sensors (sensors 1–3) and solid state sensors (gold: sensor 4, modified screen-printed electrodes (SPE) with multi-walled carbon nanotubes powder (MWCNTs): sensor 5 and gold nanoparticles GNPs-SPE: sensor 6). Potassium tetrakis has proved to be the cationic exchanger of choice which was applied to all the solid contact electrodes with nitrophenyl octyl ether as a plasticizer in a polymeric matrix of polyvinyl chloride. Incorporation of GNPs presents a superior novel performance of the electrode regarding response and sensitivity. Sensors (3, 4 and 6) showed best Nernestian response slopes of 58.19 ± 1.09, 59 ± 0.95 and 62 ± 0.98 mV/decade, respectively over a wide COD concentration range. Those proposed sensors display useful analytical characteristics for determination of COD in bulk powder, combined pharmaceutical formulation with Ibuprofen and monitoring of COD concentration in human plasma. The method was validated according to ICH guidelines. Moreover, statistical evaluation of the results was carried out compared to a reported HPLC method where the null hypothesis was confirmed.

Electrochemical Quantitative Assessment of Labetalol Hydrochloride in Pure Form and Combined Pharmaceutical Formulations

This work describes how to utilize the electrochemical technique to determine labetalol hydrochloride (Lab) in pure form and combined pharmaceutical formulation for quality control purposes. Four membrane sensors were developed using two plasticizers, dioctyl phthalate with 2-hydroxypropyl-?-cyclodextrin and ammonium reineckate (RNC) for sensors 1a and 2a, and tributyl phthalate with 2-hydroxypropyl-?-cyclodextrin and ammonium reineckate for sensors 1b and 2b as ionophores in polyvinyl chloride (PVC) matrix. Fast response and stable Nernstian slopes of 59.60, 57.58, 53.00 and 55.00 mV/decade for sensors 1a, 2a, 1b, and 2b, respectively, were obtained by developed sensors within a concentration range 10-4 M-10-2 M over pH range 2.00-5.10. Developed sensors showed good selectivity for Lab in pure form, in the presence of co-administered drugs, many of interfering ions, and excipients present in pharmaceutical formulation. No remarkable difference was detected upon the statistical comparison between the results of proposed sensors and the official method.

A novel HPLC-DAD method for simultaneous determination of alfuzosin and solifenacin along with their official impurities induced via a stress stability study; investigation of their degradation kinetics.

Stability and impurity profiling are in high demand to guarantee the potency, safety and efficacy of new formulations along with their shelf-life. In this study, stability testing of alfuzosin (ALF) and solifenacin (SOL) in their newly co-formulated capsules was conducted under different stress conditions. The obtained degradation products were structurally elucidated and found to be their official impurities, namely; ALF impurity-D and SOL impurities-A, E & I. A selective and reliable stability-indicating HPLC method was developed for assaying the cited drugs along with three of those official impurities. Chromatographic separation was accomplished within 8 minutes using a XBridge® C18 column as the stationary phase and acetonitrile : phosphate buffer (pH 8) : triethylamine (60 : 40 : 0.02, by volume) as the mobile phase at a flow rate of 1.3 mL min-1. Quantification of the analytes was performed at 210 nm using a diode array detector through which peak purity was assessed. The proposed method was validated as per ICH guidelines and it was successfully applied for the determination of the cited drugs in their combined pharmaceutical formulation with percent recoveries of 100.47 and 100.15 for ALF and SOL, respectively. Moreover, the proposed method was exploited for the assessment of the two drugs' stability in Solitral® capsules under accelerated storage conditions. The method was further extended for studying the degradation kinetics of the two drugs.