Combined Dosage Form Research Articles

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.

Comparative study of continuous wavelet transform and multivariate calibration for the simultaneous spectrophotometric determination of tamsulosin and solifenacin in combined dosage form and biological sample.

Spectrophotometry alone is not applicable for the simultaneous determination of drugs in a multi-component pharmaceutical formulation owing to their overlap. In this study, the combination of UV-Vis spectrophotometry and chemometric methods, including continuous wavelet transform (CWT) and partial least squares (PLS) was presented for the simultaneous estimation of tamsulosin (TAM) and solifenacin (SOL) in synthetic mixtures, commercial formulation, and biological sample. The simultaneous spectrophotometric determination of TAM and SOL in binary mixtures, real sample, and biological sample was performed by applying CWT and PLS approaches. In the CWT method, two various wavelet families named Daubechies (db2) at wavelength 223 nm and Biorthogonal (bior1.3) at wavelength 227 nm based on the appropriate zero crossing point were selected for TAM and SOL, respectively. The linear ranges of TAM and SOL were 0.25-4 μg/mL and 10-30 μg/mL, respectively. The limits of detection (LOD) were 0.0459 μg/mL and 0.2085 μg/mL, while the limits of quantitation (LOQ) were 0.3208 μg/mL and 0.6495 μg/mL for TAM and SOL, respectively. The average recovery values of eighteen mixtures were 98.28% and 97.79% for TAM and SOL, respectively. Also, the root mean square error (RMSE) of both components was lower than 2.3. Based on the k-Fold cross-validation in the PLS approach, the optimum number of components related to the TAM and SOL were 9 and 5 with a mean square error prediction (MSEP) of 0.0153 and 0.0370, respectively. The mean recovery values of the test set were found to be 100.09% for TAM and 99.95% for SOL where RMSE values were 0.0064 and 0.0169 for TAM and SOL, respectively. Analysis of variance (ANOVA) was applied to the results of the real sample that there was no significant difference between the proposed methods and the high-performance liquid chromatography (HPLC) as a reference technique. The result obtained revealed that the proposed methods were found to be fast, facile, economical, and precise, which provide a suitable alternative to HPLC technique for the concurrent determination of TAM and SOL in quality control laboratories. UV-Vis spectrophotometry combined with CWT and PLS was developed.Simultaneous analysis of TAM and SOL was performed using the proposed approaches.These methods were implemented on synthetic mixtures, commercial formulation, and biological sample.ANOVA test was used to compare the suggested methods and the HPLC technique.

Univariate versus multivariate spectrophotometric data analysis of triamterene and xipamide; a quantitative and qualitative greenly profiled comparative study

Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The purpose of this research is the quantitative and qualitative analysis of this binary mixture by green univariate and multivariate spectrophotometric methods. Univariate methods were zero order absorption spectra method (D0) and Fourier self-deconvolution (FSD), as TRI was directly determined by D0 at 367.0 nm in the range (2.00–10.00 µg/mL), where XIP show no interference. While XIP was determined by FSD at 261.0 nm in the range (2.00–8.00 µg/mL), where TRI show zero crossing. Multivariate methods were Partial Least Squares, Principal Component Regression, Artificial Neural Networks, and Multivariate Curve Resolution-Alternating Least Squares. A training set of 25 mixtures with different quantities of the tested components was used to construct and evaluate them, 3 latent variables were displayed using an experimental design. A set of 18 synthetic mixtures with concentrations ranging from (3.00–7.00 µg/mL) for TRI and (2.00–6.00 µg/mL) for XIP, were used to construct the calibration models. A collection of seven synthetic mixtures with various quantities was applied to build the validation models. All the proposed approaches quantitative analyses were evaluated using recoveries as a percentage, root mean square error of prediction, and standard error of prediction. Strong multivariate statistical tools were presented by these models, and they were used to analyze the combined dosage form available on the Egyptian market. The proposed techniques were evaluated in accordance with ICH recommendations, where they are capable of overcoming challenges including spectral overlaps and collinearity. When the suggested approaches and the published one were statistically compared, there was no discernible difference between them. The green analytical method index and eco-scale tools were applied for assessment of the established models greenness. The suggested techniques can be used in product testing laboratories for standard pharmaceutical analysis of the substances being studied.

Computer-Aided Design of Eco-Friendly Imprinted Polymer Decorated Sensors Augmented by Self-Validated Ensemble Modeling Designs for the Quantitation of Drotaverine Hydrochloride in Dosage Form and Human Plasma.

Computationally designed molecular imprinted polymer (MIP) incorporation into electrochemical sensors has many advantages to the performance of the designed sensors. The innovative self-validated ensemble modeling (SVEM) approach is a smart machine learning-based (ML) technique that enables the design of more accurate predictive models using smaller data sets. The novel SVEM experimental design methodology is exploited here exclusively to optimize the composition of four eco-friendly PVC membranes augmented by a computationally designed magnetic molecularly imprinted polymer to quantitatively determine drotaverine hydrochloride (DVN) in its combined dosage form and human plasma. Furthermore, the application of hybrid computational simulations such as molecular dynamics and quantum mechanical calculations (MD/QM) is a time-saving and eco-friendly provider for the tailored design of the MIP particles. Here, for the first time, the predictive power of ML is assembled with computational simulations to develop four PVC-based sensors decorated by computationally designed MIP particles using four different experimental designs known as central composite, SVEM-LASSO, SVEM-FWD, and SVEM-PFWD. The pioneering AGREE approach further assessed the greenness of the analytical methods, proving their eco-friendliness. The proposed sensors showed decent Nernstian responses toward DVN in the range of 58.60-59.09 mV/decade with a linear quantitative range of 1 × 10-7 - 1 × 10-2 M and limits of detection in the range of 9.55 × 10-8 to 7.08 × 10-8 M. Moreover, the proposed sensors showed ultimate eco-friendliness and selectivity for their target in its combined dosage form and spiked human plasma. The proposed sensors were validated in accordance with International Union of Pure and Applied Chemistry (IUPAC) recommendations, proving their sensitivity and selectivity for drotaverine determination in dosage form and human plasma. This work presents the first ever application of both the innovative SVEM designs and MD/QM simulations in the optimization and fabrication of drotaverine-sensitive and selective MIP-decorated PVC sensors.

QbD based RP-HPLC method for simultaneous determination of a emtricitabine, tenofovir diproxil fumarate and efavirenz in tablet dosage form-an application to stability indicating assay

The current studies entail Quality by Design (QbD)-enabled development of a simple, rapid, sensitive and cost-effective high-performance liquid chromatographic method for estimation of emtricitabine (EMT), tenofovir diproxil fumarate (TEN), and efavirenz (EFA) in combined dosage form. Systematic optimization was performed employing Box-Behnken design by selecting the flow rate, buffer molarity, and acetonitrile volume as the critical method parameters (CMPs) identified from screening studies, thus evaluating the critical analytical attributes (CAAs), namely, retention duration, theoretical plates, resolution, and asymmetry factor as the parameters of method robustness. The optimal chromatographic separation was achieved using acetonitrile and phosphate buffer (pH 3.0) 74.1:25.9 v/v as the mobile phase with a flow rate 0.91 mL/min, and UV detection at 260 nm. The method was validated as per the ICH recommended conditions, which revealed high degree of linearity, accuracy, precision, sensitivity and robustness over the existing liquid chromatographic methods of the drug. Studies on forced degradation under acid, basic, oxidative, photolytic, and thermal conditions revealed the drug’s well-resolved peak and the degradation products’ peaks as well.

Development of Simple VU Spectrophotometric Method for the Estimation of Bambuterol Hydrochloride in Bulk and Its Formulations

A simple, rapid and highly sensitive spectrophotometric method has developed for the estimation of Bambuterol hydrochloride in bulk and marketed tablet dosage form. In distilled water, Bambuterol showed absorbance at 264nm. Linearity was observed in the conc range of 200-1000 μg/ml (r2 = 0.9990). The assay results were found to be in a good agreement with label claim. The recovery studies were carried at 3 different levels i.e, at 100%, 150%, 200%. The accuracy of the method was conformed by recovery studies of tablet dosage forms and was found to be 96.43% for bambuterol hydrochloride. The method was validated stastically and by good recovery with % RSD is less than 2Thus the proposed method was found to be rapid, specific, precise, accurate and cost-effective quality control tool for the routine analysis of bambuterol hydrochloride in bulk and combined dosage form.

RP-HPLC Method Development for Simultaneous Estimation of Brimonidine Tartrate and Timolol Maleate in Ophthalmic Preparation

Introduction: A simple, precise, rapid, and reproducible RP-HPLC method is developed for the simultaneous estimation of brimonidine tartrate and timolol maleate present in ophthalmic dosage forms.
 Method: Gradient RP-HPLC is carried out at 35℃ on column C18 (25 cm X 4.6 mm, 5 µm) with mobile phase a ACN and buffer (25 ml ACN & 475 ml buffer) and mobile phase B water and ACN (37.5 ml water & 212.5 ml ACN) at a flow rate of 1.2ml/min. detection is carried out using DAD detector at 248 nm. Parameter such as linearity, accuracy, precision, specificity, LOD, LOQ and robustness are studied as per ICH guidelines Q2 (R1). 
 Results: The linearity range of Brimonidine tartrate and Timolol maleate are 10-50 µg/ml and 4-20 µg/ml. The accuracy for both Brimonidine Tartrate and Timolol Maleate are in range of 100-101%. The RSD for Brimonidine Tartrate and Timolol Maleate are less than 2 for precision, specificity, robustness respectively. 
 Conclusion: This RP-HPLC method can be highly suitable for analysis of brimonidine tartrate and timolol maleate without interference in combined dosage form.

Development & determination of UV method for sildenafil & fluxetine in bulk drug & in formulation

A simple, rapid, precise and highly selective spectrophotometric method was developed for simultaneous estimation of Sildenafil citrate and Fluoxetine Hydrochloride in tablet dosage form. This method, involves the measurement of absorbances of Sildenafil citrate and Fluoxetine Hydrochloride at the wavelengths of 282nm (λmax of Sildenafil citrate) and 249 nm (λmax of Fluoxetine Hydrochloride). Methanol was used as solvent. Linearity was observed in the concentration range of 10-18µg/ml for Sildenafil citrate and 3-8ug/ml. Fluoxetine Hydrochloride. The accuracy of the method was confirmed by recovery studies of tablet dosage forms and was found to be 98.1% and 99.2% for Sildenafil citrate and Fluoxetine Hydrochloride respectively. The method showed good reproducibility and recovery with % RSD less than 2. Thus, the proposed method was found to be rapid, specific, precise, accurate and cost-effective quality control tool for the routine analysis of Sildenafil citrate and Fluoxetine Hydrochloride in bulk and combined dosage form. A rapid and simple derivative spectrophotometric method was developed for simultaneous determination of Sildenafil citrate and Fluoxetine Hydrochloride in tablet dosage form. This method involves second order derivative spectroscopy using 282 nm and 249 nm as zero crossing points for Sildenafil citrate and Fluoxetine Hydrochloride respectively in methanol. Linearity was observed in the concentration range of 10-18µg/ml for Sildenafil citrate and 3-8ug/ml for Fluoxetine Hydrochloride. The accuracy of the method was found to be 98.21% and 99.2% for Sildenafil citrate and Fluoxetine Hydrochloride respectively. The method showed good reproducibility and recovery with % RSD less than 2.Thus, the proposed method was found to be rapid, specific, precise, accurate and cost-effective quality control tool for the routine analysis of sildenafil citrate and Fluoxetine Hydrochloride in bulk and combined dosage form. A selective, precise, isocratic and accurate stability indicating reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of Sildenafil citrate and Fluoxetine Hydrochloride in the tablet dosage form. The method was validated for the linearity, accuracy, precision, robustness, system suitability as per ICH guidelines. Sildenafil citrate and Fluoxetine Hydrochloride were found to be linear in the range of 10-100 and 10-18µg/ml and 3-8ug/ml with the recoveries of 98.6% and 99.2%. The method was also applied for the determination of sildenafil citrate and Fluoxetine Hydrochloride in the presence of their degradation products formed under variety of stress conditions.

Development of Analytical Technique for Dichlofenac Sodium and Ibuprofen Utilizing UV Visible Spectroscopy and AUC Method

The purpose of this work was to create an analytical method combining UV visible spectroscopy and the AUC method for the simultaneous determination of diclofenac sodium and ibuprofen in their combination dosage form. The medications’ UV spectra were captured between 200 and 400 nm, and the calibration curves were built using AUC values for diclofenac sodium and ibuprofen at 274 nm and 222 nm, respectively. The developed method’s linearity, precision, accuracy, limit of detection, and limit of quantification were all validated in accordance with ICH recommendations. The findings demonstrated that the approach was linear, exact, accurate, and sensitive for the measurement of ibuprofen and diclofenac sodium. Without any excipient interference, the suggested approach was effectively used to determine the two medicines in their combination dose form. The created approach is straightforward, accurate, and cost-effective, and it may be utilised for regular analysis of ibuprofen and diclofenac sodium in their combination dose form.

A combination preparation based on antibiotic, cluster silver and bacteriophage for treatment of infectious diseases caused by <i>Staphylococcus aureus</i> and <i>S. aureus</i> MRSA

The problems of bacterial infections in medicine and veterinary medicine require careful study and rapid solution. Due to continuous and, in some cases, irrational use of antibiotics, the efficiency of their effect on host has been noticeably decreasing; moreover, resistance to antibacterial drugs is steadily growing, antibiotic-resistant strains emerge, which are not amenable to conventional medical treatment. The unprecedented rise of pathogenic bacteria resistance to antibiotics requires generation of new drugs to combat them. One of the ways to increase the effectiveness of antibiotic therapy is to use combination drugs. Combination dosage forms provide an increased therapeutic effect and should not be toxic to the body. To overcome the microbial resistance reducing host burden of antibiotics, we proposed a combination preparation based on antibiotic, cluster silver and specific bacteriophage for treatment of infectious diseases caused by S. aureus, including MRSA strains. Each component has already proven in the treatment of pathogen-caused infectious diseases. But while using this combination agent, it became possible to reduce the amount of antibiotic and get rid of antibiotic-resistant and phage-resistant forms of bacteria. The study showed the effectiveness of the combination preparation on S. aureus MRSA bacteria, while reducing the amount of antibiotics in proposed composition by 24 times compared to use of antibiotic alone. The efficacy of the preparation containing was as follows: 10 mg/ml gentamicin, 7 mg/ml cluster silver and 106 BOV/ml bacteriophage, on S. aureus MRSA bacteria in suspension is comparable to the effectiveness of gentamicin with a concentration of 40 mg/ml. For S. aureus 209 and S. aureus ssp. bacteria with reduced resistance to antibiotics, the use of two-component compositions (antibiotic + cluster silver; antibiotic + bacteriophage) also allowed to reduce the antibiotic concentration by 23 times. It should be noted that with a constant amount of antibiotic, increasing the amount of cluster silver by 45 times, there is a rise in bactericidal properties of the resulting preparations. Repeated introduction of drug dose allows to achieve a marked decrease in level of pathogenic microorganisms in the suspension studied. This drug has no limitations depending on the state and degree of microbial resistance.

Second-Order Derivative Spectrophotometric Method for Simultaneous Estimation of Azilsartan Medoxomil and Cilnidipine in Combined Dosage Form

Second-Order Derivative Spectrophotometric Method for Simultaneous Estimation of Azilsartan Medoxomil and Cilnidipine in Combined Dosage Form

Development and Validation of Stability‐Indicating HPLC Method for Simultaneous Quantification of Vardenafil and Dapoxetine in Bulk and in Combined Dosage Form

AbstractAn understanding of drug product degradation issues is needed to advise stable formulation and provide a reasonable shelf‐life evaluation for all drug products. For this purpose, we have developed and validated a novel HPLC method for assessing the stability of vardenafil and dapoxetine in a combined pharmaceutical dosage form. The chromatographic separation was accomplished on a ProntoSIL C18 KROMA PLUS column (250×4.6 mm, 5 μm). The column was run under isocratic conditions with a 2.0 mL/min flow rate. The mobile phase was made up of methanol and 20 mM potassium dihydrogen phosphate at 45 : 55 (v/v), which was adjusted to pH 3.0 with phosphoric acid; these two drugs were eluted at retention times of 5.33 and 9.91 min for vardenafil and dapoxetine, respectively. The proposed method shows a linearity of 1–50 ug/ml with a regression of 0.9999 for both drugs. The method was validated for accuracy, precision, linearity, specificity, and sensitivity. The developed HPLC method has been successfully implemented to analyse dapoxetine and vardenafil in tablets. Furthermore, the stress degradation experiments were conducted on the bulk powder of vardenafil and dapoxetine following the International Council for Harmonization (ICH) recommendations.

Construction of a Zinc Oxide Nanorod-Modified Coated Wire Electrode for Potentiometric Determination of Levocetirizine Dihydrochloride in Its Pure and Combined Form.

Coated wire electrodes (CWEs) are considered the most effective and selective type of ion- selective electrodes because of the electroactive materials which are used in surface modification. This study aims to construct the first potentiometric method for analysis of levocetirizine (LVZ) in its combination form with montelukast (MON) drug. A novel potentiometric sensor which consists of a silver wire coated with zinc oxide (ZnO) nanorod modified with a polymeric membrane (combining β-cyclodextrin and tetraphenyl borate, and plasticized with di-butyl phthalate) was constructed for the determination of LVZ·2HCl in its pure form and its combination dosage form. The fabricated sensor exhibited a linearity range of 5 × 10-6-1 × 10-2 mol/L with a Nernstian slope 57.88 mV/decade over the pH range 2-4.5. The effect of temperature on the constructed sensor was studied and it was found that the electrode worked effectively over 10-50°C. The electrode showed a fast response time and the lifetime of the electrode was found to be 72 days without significant change in the Nernstian slope value. The selectivity of the electrode toward LVZ was estimated in the presence of some obstructive ions. The method was validated according to International Council for Harmonisation of Technical Requirments for Registration of Pharmaceuticals for Human Use (ICH) rules and applied to the determination of LVZ in its pure and combined pharmaceutical dosage forms. This article introduces the synthesis of the first coated wire electrode modified with zinc oxide (ZnO) nanorods for the determination of the drug levocetirizine. The results demonstrate the ability of electrochemical methods to analyze drugs in combination. The presented method excels over the other analytical methods in terms of sensitivity, selectivity, and simplicity.

Comprehensive and Validated Chromatographic Techniques for the Estimation of Lercanidipine Hydrochloride and Atenolol in Bulk and Combined Dosage Form in the Presence of Lercanidipine Degradation Products with LC/MS Characterization.

Two rapid, smart and validated stability indicating HPLC and TLC techniques were developed to determine atenolol (ATE) and lercanidipine HCl (LER) simultaneously in their pharmaceutical formulation. HPLC chromatographic separation was implemented by using Microsorb C18 (250 × 4.6mm, 5μm) column, with mobile phase of acetonitrile and 20mM potassium dihydrogen phosphate buffer pH3.5 adjusted by orthophosphoric acid in the ratio of (65:35, v/v) at a flow rate of 1.2mL/min at 240nm also the injection volume adjusted to be 30μL. These selected conditions effectively separated ATE and LER at a retention time of 2 and 6.7min, respectively, by isocratic elution mode without any interference from the obtained degradation products of LER. The densitometric determination was performed by using precoated silica gel 60F254 aluminum plates and chloroform, methanol and triethylamine (11.3:1.3: 0.3, by volume) as a developing system. The detection wavelength for simultaneous estimation of both drugs was 240nm in the presence of the oxidative product of LER. The RF values for ATE and LER were 0.22 and 0.78, respectively. The calibration curves of both techniques were constructed with linearity ranges of (5-55)μg.mL-1 and (1-55)μg.mL-1 for both ATE and LER, respectively, for HPLC determination. While for TLC, the linearity ranges were (1-4)μg/band and (0.2-1.4)μg/band for ATE and LER, respectively. LER degradation products were characterized using UPLC/MS and the suggested mechanisms and degradation pathways were introduced.

Method Development and Validation of Fluconazole and Ivermectin in pure and Combined Dosage form using UV by Q- absorption ratio and Vierotd’s method

Multicomponent analysis involves simultaneous estimation of drug substances in combined dosage form. A comparative study between Q-Absorption ratio technique and Simultaneous Equation Method has been established for effective implication of the developed method. Numerous trials were performed as a part of solvent selection, both the drugs under study Fluconazole (FLN) and Ivermectin (IVR) have shown good solubility in methanol (Spectroscopic Grade). The absorption maxima (λmax) were found to be 261nm for FLU and 245nm for IVR respectively. Both the drugs were showing same extinction coefficient (Isosbestic point) at 261nm. A comparative study is proposed to be established for simultaneous equation and Q-absorption ratio method. Between the concentration and absorbance, calibration curves revealed a linear relationship. The regression line equation was established and identified r2 for Fluconazole and Ivermectin is 0.999 and 0.999. Fluconazole and Ivermectin were assessed by the validated method when each of the drug individually subjected to various stress conditions like concentrated acidic, basic, peroxide, excessive light and thermal. For estimation, the suggested approach was used for drug content in locally available marketed formulations which has proven successful for routine analysis of the same with the application of vierotd’s as well as Q-absorption method.

Deduction of the operable design space of RP-HPLC technique for the simultaneous estimation of metformin, pioglitazone, and glimepiride

A reversed-phase RP-HPLC method was developed for the simultaneous determination of metformin hydrochloride (MET), pioglitazone (PIO), and glimepiride (GLM) in their combined dosage forms and spiked human plasma. Quality risk management principles for determining the critical method parameters (CMPs) and fractional factorial design were made to screen CMPs and subsequently, the Box–Behnken design was employed. The analytical Quality by Design (AQbD) paradigm was used to establish the method operable design region (MODR) for the developed method depended on understanding the quality target product profile (QTPP), analytical target profile (ATP), and risk assessment for different factors that affect the method performance to develop an accurate, precise, cost-effective, and environmentally benign method. The separation was carried out using a mobile phase composed of methanol: 0.05 M potassium dihydrogen phosphate buffer pH 3.7 with 0.05% TEA (78:22, v/v). The flow rate was 1.2 mL/min. DAD detector was set at 227 nm. Linagliptin (LIN) was used as an internal standard. The proposed method was validated according to The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The assay results obtained by using the developed method were statistically compared to those obtained by the reported HPLC method, and a satisfying agreement was observed.

A Novel, Sustainable, and Eco-Friendly Spectrophotometric and Chemometric Approach for Determination of Severely Overlapped Spectrum via Unified Regression Equation: Greenness and Whiteness Assessment.

Nebivolol and valsartan (VAL) in combination with each other successfully control blood pressure and improve hypertension patient outcomes. To develop and validate innovative, simple, and sustainable spectrophotometric methods for the simultaneous analysis of nebivolol and valsartan. The new modified difference amplitude modulation (MD-AM) method uses only unified regression equation and does not require any resolution techniques. Other different approaches were also applied for the determination of the same mixture including univariate and multivariate spectrophotometric methods. The multivariate methods were PLS and PCR, whereas the univariate methods were derivative ratio (DD1), ratio difference (RD), constant center (CC), constant center spectrum subtraction (CC-SS), constant value coupled with amplitude difference (CV-AD), advanced concentration value (ACV), and amplitude difference (AD). The proposed methods use a green solvent; thus, the environmental impact of the presented procedures was evaluated qualitatively and quantitatively using six well-known evaluation tools. All methods were applied successfully for the analysis of the studied drugs in their bulk powder, pharmaceutical dosage form Byvalson®, and in vitro release at intestinal pH (7.4) using a USP dissolution tester. Results obtained were compared statistically with the reported method and with each other using a one-way ANOVA statistical test, and no significant differences were found. All green and white analytical chemistry evaluation tools results confirm the safety, sustainability, and cost-effectiveness of the approaches, indicating that the methods are regarded green and sustainable. Results were agreeable, encouraging their applicability in quality control laboratories for dosage form and making these methods an eco-friendly substitute for the analysis of this combined dosage form and for evaluating the dissolution profile. For the first time, a severely overlapped spectrum was determined using a unified regression equation without the need of extended part or zero contribution regions by the novel method MD-AM. The proposed methods are the first study of in vitro dissolution profiling of nebivolol hydrochloride (NEB) and VAL and the first sustainable and green methods applied without compromising the analytical criteria.

Development of thin layer chromatographic densitometric method for simultaneous quantification of Ivabradine HCl and Bisoprolol fumarate

AbstractThe literature review reveals that no thin‐layer chromatographic method has been developed for the simultaneous estimation of Bisoprolol fumarate and Ivabradine HCl in the combined dosage form. A sensitive, precise, accurate, and robust thin‐layer chromatographic method was developed and validated for the simultaneous quantification of a newer combination of Bisoprolol fumarate and Ivabradine HCl used in the treatment of angina, according to the International Council for Harmonization Q2 (R1) guideline. The stationary phase was pre‐coated silica gel aluminum plate 60 F254 and toluene‒methanol‐triethylamine (9:1:0.1, v/v/v) was used as the mobile phase. A common detection wavelength of 279 nm was selected for the simultaneous quantification of Bisoprolol fumarate and Ivabradine HCl. The method was validated for different parameters like linearity, precision, accuracy, robustness, the limit of detection, and the limit of quantification as per the International Council for Harmonization guidelines. The correlation coefficients (r2) for Bisoprolol fumarate and Ivabradine HCl were found to be 0.9976 and 0.9965, respectively. The mean percentage recoveries for Bisoprolol fumarate and Ivabradine HCl were found to be 99.19%–101.70% and 98.71%–101.86%, respectively. As per the International Council for Harmonization Q2 (R1) guideline, the proposed TLC method was repeatable and selective as per statistical analysis and it can be used for simultaneous estimation of Bisoprolol fumarate and Ivabradine HCl in bulk and formulation.

SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS DETERMINATION OF SULPHACETAMIDE SODIUM AND PREDNISOLONE ACETATE IN OPHTHALMIC FORMULATION

A simple, precise, accurate, and rapid derivative spectrophotometric approach for the simultaneous quantification of sulfacetamide sodium (SUL) and prednisolone acetate (PRE) in the combined dosage form has been established and validated. The wavelengths selected for analysis are 230 nm (ZCP of SUL) and 244 nm (ZCP of PRE) for SUL and PRE, respectively. The suggested technique has exhibited linearity for a concentration range of 2–6 µg mL-1 for PRE and 5–15 µg mL-1 for SUL, respectively. Both medications had percentage recoveries that varied from 99.41 to 101.8. The suggested approach has been validated according to ICH guidelines [Q2(R1)] for linearity, LOD, LOQ, accuracy and precision. The proposed method can be successfully utilized to analyze SUL and PRE concurrently in ocular formulations.

Stability Indicating HPLC Method for Simultaneous Assessment of Clopidogrel Bisulfate and Aspirin: Development and Validation

Objectives: The efforts were made to develop a HPLC analytical method for the simultaneous quantitative estimation of aspirin and clopidogrel and aim to identify and estimate the degradation of the drugs under the various stress conditions recommended by ICH guideline. Materials and Methods: The separation of two drugs were done by using LC-20AD liquid chromatograph having SPD-20A UV-vis detector on C18 (4.6 x 150 mm) column which was connected with loop 20μl and with HPLC-Dell system. Mobile phase consisted of acetonitrile: buffer in the ratio of 350:650 v/v. Flow rate was 1.3 ml/min and detection were done at 220 nm. Proportions of solvents and adjustment of mobile phase was carried out by screening. Results: The chromatographic separation of aspirin was noted at 4.299 minutes with average USP tangent of 8332.046 and clopidogrel was at 12.706 min with average of 11886.0397 tangent. A linear correlation was observed between concentration of aspirin and clopidogrel with their dilutions i.e r2 = 0.9986 and 0.9996 respectively. The outcome of study, with limit of detection 0.058 and 0.078 μg/ml and limit of quantification 0.117 and 0.156 μg/ml, for aspirin and clopidogrel revealed the repeatability, reproducibility and robustness of the method. Stability indicating parameters were tested by ICH guideline. Conclusion: It is concluded that the method is linear, reproducible, robust, rugged and stability-indicating for simultaneous calculation. It can be used as a routine quality control method for combined pharmaceutical dosage form and for its kinetic studies.