Combined Dosage Form Research Articles

Spectral analysis of severely overlapping spectra based on newly developed mathematical filtration techniques and ratio spectra manipulations: An application to the concurrent determination of dapoxetine and sildenafil in combined dosage form

BackgroundDapoxetine hydrochloride (DAP) and sildenafil citrate (SIL) have proven clinically effective in the treatment of comorbid conditions like erectile dysfunction and premature ejaculation. The analysis of DAP and SIL combinations represents a challenge because of the severe overlap of these compounds’ spectra. Six newly developed methods were proven effective for resolving such a challenging overlap. They also exhibited the advantage of simplicity as they depend on the zero-order spectrum and only require simple mathematical handling. ObjectiveWe suggested six simple, precise, and sensitive spectrophotometric methods based on mathematical filtration techniques and ratio spectra manipulations to resolve the spectra of DAP and SIL in their bulk and combined pharmaceutical dosage form and estimate the relevant individual concentrations. MethodsThe first three methods were based on the zero-order range and involved modest mathematical manipulations. They are the induced dual-wavelength, Fourier self-deconvolution, and absorptivity factor spectrophotometric methods. Three other methods that are based on ratio spectra manipulation were developed: ratio difference, mean centering of the ratio spectra, and derivative ratio spectrum. ResultsWe determined the performance of the suggested methods for estimating DAP and SIL in their laboratory mixtures and their combined pharmaceutical dosage form. The linear ranges for DAP and SIL were 1–40 µg/ml and 2–60 µg/ml, respectively. The detection limits were in the 0.18–1.10 µg/ml range for DAP and in the 0.68–1.11 µg/ml range for SIL. The developed methods were validated as per the ICH guidelines for linearity, detection limit, quantitation limit, selectivity, precision, and accuracy. Normal probability, interval, and Tukey’s simultaneous significant difference plots were utilized to confirm and better visualize the analysis of variance test results. Statistically, no significant difference was observed to exist between results obtained from the hereby developed and the previously reported methods.

First-order derivative spectrophotometric estimation of gemifloxacin mesylate and ambroxol HCl in tablet dosage form

Aim of present work was to develop and validate a simple, precise and accurate uv-vis spectrophotometric method for the simultaneous estimation of gemifloxacin mesylate (GEMI) and ambroxol HCl (AMB) in their combined tablet dosage form. The method is based on first-order derivative spectroscopy. For determination of sampling wavelengths, each of GEMI and AMB were scanned in the wavelength range of 200–400 nm in the spectrum mode and sampling wavelengths were selected at 360 nm (zero crossing of GEMI) where AMB showed considerable absorbance and at 221.6 nm (zero crossing of AMB) where GEMI showed considerable absorbance. The linearity was obtained in the concentration range of 32-192 µg/ml for GEMI and 7.5-45 µg/ml for AMB. The correlation coefficients were found to be 0.9987 and 0.9992 for GEMI and AMB, respectively. The method was validated as per ICH guidelines. Mean recoveries were found satisfactory. All the data of validation study was found to be satisfactorily. The proposed method can be applied for simultaneous estimation of both the drugs

Chemometry‐assisted UV‐spectrophotmetric methods for the simultaneous determination of paritaprevir, ritonavir, and ombitasvir in their combined tablet dosage forms: A comparative study

AbstractThe ternary mixture under study is a recent hepatitis‐C antiviral medicine composed of three new directly acting antiviral drugs, namely, ombitasvir, paritaprevir, and ritonavir. They are co‐formulated as a single‐dose combined tablet dosage form. With more than 170 million infected patients worldwide, a large production scales of antivirals medicine is expected, and hence, new simple and fast methodologies are required to cover millions of analyses that are done routinely in the different pharmaceutical quality control and research laboratories. Ultraviolet spectrophotometry represents sensitive, fast, and cheap tool of analysis in all research and quality control laboratories that can cover the massive quality control of these regimens. However, the simultaneous determination of these three drugs using multivariate chemometric methods represents a high challenge as their spectra are strongly overlapping besides the large difference in their potency within the same tablet. In this research paper, four new different multivariate chemometric methods were developed for their simultaneous determination, namely, classical least square (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm‐partial least squares (GA‐PLS) techniques. The validated methods do not require extraction, separation, or derivatization steps. A comparative study was conducted among the four developed methods. All methods provided satisfactory results, whereas GA‐PLS showed better analytical performance as it had the lowest error with good higher correlation coefficient. The methods were applied in the simultaneous determination of the three drugs in pure form and in their combined tablet dosage form. The comparison confirmed agreement of the values obtained for all techniques.

Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Lansoprazole, Clarithromycin and Tinidazole in Combined Dosage Form

Analytical chemistry is one of the supreme branches of science which deals with the separation, identification and quantification of various natural and chemical compounds. It includes both qualitative and quantitative analysis. Quantitative analysis is having importance from the point of pharmaceutical chemistry. Quantification methods include chromatographic techniques, spectrophotometery, fluorimetery etc. One of the most popular method for quantitative analysis is High Performance Liquid Chromatography (HPLC). In this article, a reverse phase – HPLC method was developed for the simultaneous determination of Lansoprazole, Clarithromycin and Tinidazole in combined dosage form and validation of the developed method. The development of method includes selection of mobile phase, chromatographic method and wavelength whereas validation involves the parameters like linearity, accuracy, precision, Limit of detection (LOD), Limit of Quantification (LOQ), robustness, system suitability of the developed method. The result showed that the developed method is best fitted to the simultaneous determination of Lansoprazole, Clarithromycin and Tinidazole and validated as per standards.

Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Methionine, Pyridoxine Hydrochloride and Nicotinamide in Combined Dosage Form

Analytical chemistry is one of the important branches of science which deals with the study of separation, identification and quantification of various natural and chemical compounds. Quantitative analysis is having supremacy from the point of pharmaceutical chemistry. Quantification methods include chromatographic techniques, spectrophotometery, fluorimetery etc. One of the accurate method for quantitative analysis is High Performance Liquid Chromatography (HPLC). In the present manuscript, a reverse phase – HPLC method was developed for the simultaneous determination of Methionine, Pyridoxine hydrochloride and Nicotinamide in combined dosage form and validation of the developed method. The development of method includes selection of mobile phase, chromatographic method and wavelength whereas validation involves the parameters like linearity, accuracy, precision, Limit of detection (LOD), Limit of Quantification (LOQ), robustness, system suitability of the developed method. The result showed that the developed method is best suited to the simultaneous determination of Methionine, Pyridoxine hydrochloride and Nicotinamide and validated as per standards.

Validated RP-HPLC Method for Simultaneous Estimation of Atenolol, Hydrochlorothiazide and Losartan Potassium in Bulk and Pharmaceutical Dosage Form

A simple, specific, accurate, and precise reverse phase high performance liquid chromatographic (RP-HPLC) method was developed for the simultaneous estimation of Atenolol, Hydrochlorothiazide and Losartan potassium in bulk and pharmaceutical dosage form. The separation was carried out using Hypersil C18, 250 ×4.6 mm, 5µm column with mobile phase consisted mixture of Acetonitrile and Potassium dihydrogen ortho phosphate buffer in the ratio of 40:60 (V/V) delivered at a flow rate of 1.5 mL / min and effluents were monitored at 225 nm. The selected chromatographic conditions were effective separation of these drugs. And the retention times of Atenolol, Hydrochlorothiazide and Losartan potassium were found to be 1.46, 2.21 and 3.30 min respectively. The proposed method was found to be linear in the range of 50-150 μg/mL,12.5-37.50 μg/mL, and 50-150 μg/mL for Atenolol, Hydrochlorothiazide and Losartan potassium respectively. The recovery of drugs was found to be 97.56 %, 97.72 % and 98.06 % respectively. The proposed method was validated as per ICH guidelines and it was found to be accurate, precise and robust, and it was applied to the estimation of Atenolol, Hydrochlorothiazide and Losartan potassium in combined tablet dosage form and it can also be used for routine quality control analysis of these drugs in biological samples either alone or in combined pharmaceutical dosage forms.

Simultaneous Estimation of Amlodipine Besylate and Candesartan Cilexitil by HPTLC Method in their Combined Dosage Form

Simultaneous Estimation of Amlodipine Besylate and Candesartan Cilexitil by HPTLC Method in their Combined Dosage Form

Eco-friendly RP-HPLC and HPTLC Methods for Simultaneous Determination of Tamsulosin Hydrochloride and Deflazacort in the Presence of 21-Hydroxy Deflazacort and Testing the In-vitro Dissolution of the Combined Dosage Form via RP-HPLC Method

Two Eco-friendly methods based on chromatographic separation were developed for simultaneous assay of Tamsulosin HCl and Deflazacort in their binary mixture. Green mobile phase which consists of mixture of ethanol and dilute acetic acid was employed for both developed methods. The first method was reversed phase high performance liquid chromatography (RP-HPLC) with a photodiode array (DAD) detection for quantification of both drugs at wavelengths of 225 and 245 nm over a linearity range of 0.20–100 and 0.50–200 μg mL−1 for Tamsulosin HCl and Deflazacort, respectively. The second method was high performance thin layer chromatography (HPTLC) for separation and detection of the drugs by densitometry at 225 nm in the range of 0.30–4.0 and 0.70–5.0 μg band−1 of Tamsulosin HCl and Deflazacort, respectively. The proposed methods were validated to comply with ICH guidelines. Regarding the high liability of Deflazacort to be degraded to its active metabolite: 21-Hydroxy Deflazacort, the suggested methods were assessed for their applicability to determine the two drugs in the presence of 21-Hydroxy Deflazacort and evaluated based on chromatographic system suitability parameters. Application of the proposed methods was performed for determination of Tamsulosin HCl and Deflazacort in their combined tablet dosage form besides monitoring its in-vitro dissolution patterns by the RP-HPLC method. The greenness of the suggested methods was evaluated using the Analytical Eco-scale and compared with the other official or reported methods for determination of cited drugs.

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE ESTIMATION OF ESCITALOPRAM OXALATE AND FLUPENTIXOL DIHYDROCHLORIDE IN COMBINED DOSAGE FORM AND PLASMA

Objective: The objective of the study was to develop a simple and rapid chromatographic method for quantification of escitalopram oxalate and flupentixol dihydrochloride in combined dosage form and plasma.
 Methods: The separation was achieved with a sun fire C8 [150×4.6 mm] 3.5 µm column with an isocratic mobile phase containing a mixture of potassium dihydrogen orthophosphate buffer: methanol: acetonitrile [30:60:10 v/v/v] pH adjusted to 11. The flow rate of the mobile phase was 1.5 ml/min with a Photodiode array [PDA] detection at 230 nm.
 Results: The HPLC method was developed and validated with respective linearity, accuracy, and precision, detection of limit, robustness, and specificity. The precision of the results stated as the relative standard deviation was below 2 %. The calibration curve was linear over a concentration range from 10-50 µg/ml for escitalopram oxalate and 1-5 µg/ml for flupentixol dihydrochloride with a correlation co-efficient 0.994 and 0.977 respectively. The accuracy of the method was demonstrated at levels in the range of 100 % and 120 % of the specification limit. The recovery of escitalopram oxalate and flupentixol dihydrochloride was found to be in the range of 90 % to 88 %, respectively. The lowest detection limits were found to be 2 µg/ml for escitalopram oxalate and 0.1 µg/ml for flupentixol dihydrochloride. The lowest quantification limits were found to be 5 µg/ml of escitalopram oxalate and 0.5 µg/ml of flupentixol dihydrochloride.
 Conclusion: The developed method was validated for linearity, accuracy, precision, the limit of detection and quantification, specificity. The method was applied successfully for the determination of escitalopram oxalate and flupentixol dihydrochloride in the combined dosage form and plasma.

Simultaneous estimation of troxerutin and calcium dobesilate in presence of the carcinogenic hydroquinone using green spectrofluorimetric method.

In the present study, we conducted two facile and highly sensitive spectrofluorimetric approaches in order to quantify the vasoprotective agents; troxerutin (TROX) and calcium dobesilate (DOB) in the presence of hydroquinone (HQ) (as a highly toxic impurity and potential degradation product of DOB) in commercial formulations and human plasma. The first approach relies simply on using ethanol as an eco-friendly solvent for the estimation of DOB at 345 nm after being excited at 305 nm. The linearity was carefully investigated between DOB concentration and the relative fluorescence intensity in the range of 0.05–0.8 µg ml−1. Due to the high method simplicity and sensitivity, applying the first approach to quality control analysis and spiked human plasma samples with mean % recoveries 100.74 ± 3.71 adds another merit. The second approach involved rapid conventional fluorimetric estimation of ethanolic TROX solution in TROX/DOB combined dosage forms at 455/350 nm (emission/excitation) with a linear calibration chart covering the range of 0.1–1.2 µg ml−1. Moreover, the second approach involved a comprehensive study in a trial to solve the problem of superposition of DOB and HQ graph adopting the first derivative synchronous fluorimetric mechanism in ethanol at Δλ = 60 nm. Therefore, DOB was measured at 286 and 323 nm, while HQ could be quantitated at 301 nm. The Beer–Lambert Law has complied over the ranges of 0.1–1.0 and 0.02–0.4 µg ml−1 for DOB and HQ, respectively. Guidelines adopted by the International Council of Harmonization (ICH) were used to validate the target approaches. The developed methods are more convenient for routine quality control laboratory instead of the time-consuming and sophisticated reported techniques. Moreover, different aspects of evaluating the greenness of the proposed approaches were conducted to have a complete image of their environmental impact.

Simultaneous Determination of Cefixime, Cefdinir and Clavulanic Acid by High Performance Liquid Chromatography

In this study, two cephalosporin groups of antibiotics (cefepime and cefixime) and their combinations with clavulanic acid, beta lactamase inhibitor, were simultaneously analyzed by HPLC method. The optimum separation was carried out on MZ C18 column (250 × 4.6 mm; i.d. 5 μm) with mobile phase consisting of an acetonitrile – 0.01% phosphoric acid (pH 2.5) (15 : 85, v/v) binary mixture. Detection was performed using a diode array detector at 228 nm. Under these experimental conditions, the analysis was accomplished in about 10 min. The developed method is specific, linear, sensitive, accurate, precise, and robust. The method was completely validated showing satisfactory data for all the parameters tested. Finally, the proposed method was successfully applied to two combined pharmaceutical dosage forms containing cefepime with clavulanic acid and cefixime with clavulanic acid.

Development and Validation of RP-HPLC Method for the estimation of Sofosbuvir and Ledipasvir in combined dosage form

Nowadays scientists aim at developing generic and specific methods for drugs in combined pharmaceutical dosage forms. The main aim was to develop and carry out validation using precision and accuracy for Sofosbuvir and Ledipasvir by applying RP-HPLC method. The dosage form in fixed combination of Sofosbuvir-Ledipasvir helps in effective treatment of genotypes of chronic hepatitis C virus. This combination of Sofosbuvir-Ledipasvir was the first FDA approved direct acting antiviral to treat hepatitis C. Both the drugs were optimized using mobile phase as acetonitrile: 0.1% orthophosphoric acid (55:50v/v) with pH 3.0. The mobile phase was optimized at maximum wavelength of 283nm. The separation was achieved using C18 Cosmosil (4.6 x 250mm) column with a particle size of 5µ. The method was specific eluting retention times of 3.7 for Sofosbuvir and 6.0 for Ledipasvir. Intra and interday precision was carried and %RSD was found to be less than 2%. The results were found to be accurate with percentage recovery of 99.76% and 99.10% for Sofosbuvir and Ledipasvir respectively. Linearity was carried out in the concentration ranging from 40-200µg/mL and 9-45µg/mL for Sofosbuvir and Ledipasvir respectively. Both the drugs showed the regression coefficient of 0.999. Deliberate changes in flow rate, pH and wavelength were made and found that method was robust. The developed method was found to be accurate, simple, specific, robust and precise for the simultaneous estimation of Sofosbuvir and Ledipasvir in tablet dosage form.

Different chemometric assisted approaches for spectrophotometric quantitative analysis of lesinurad and allopurinol

Three chemometric assisted spectrophotometric approaches were designed for precise quantitative analysis of lesinurad and allopurinol, in their recently FDA approved combination pharmaceutical dosage form. By utilizing the recorded absorption spectral data of lesinurad and allopurinol mixtures, principle component regression, partial least squares and genetic algorithm partial least squares were developed and compared for the spectrophotometric quantitative analysis of the cited drugs in their binary mixture. Experimental design for different concentrations of the studied drugs was done based on the spectral sensitivity and the commercial ratio of the two drugs in the combined pharmaceutical dosage form. Optimization of the described models was done using five-levels, two factors experimental design principle. Quantitative assay of the two drugs in Duzallo® tablet was successfully done and the data obtained was statistically compared with the results of another published HPLC quantitative analytical method.

Determination of lornoxicam by UV spectroscopic method in bulk and combined dosage form

Objective: In the present study a suitable UV Spectroscopic method was developed and validated for Lornoxicam determination in bulk and combined dosage form. Methods: UV Spectrophotometric method was performed at 376nm and samples were prepared with a solution of 0.1N HCl, validation parameters like accuracy, precision, LOD, LOQ, recovery study and range were determined. Results: The linearity demonstrated a correlation coefficient of 0.9992 various validation parameters like accuracy, precision, LOD, LOQ, recovery study and range were found to be within the specified range. Conclusion: The proposed method was simple, rapid, precise, accurate and sensitive and can be used for routine analysis of Lornoxicam in bulk and combined dosage form.

Simultaneous Estimation of Solifenacin Succinate and Tamsulosin Hydrochloride in Combined Dosage Form by Using First Order Derivative Spectrophotometric Method

Using first-order derivative techniques, a simple accurate and precise Ultraviolet spectrophotometric method was developed for the determination of solifenacin succinate and tamsulosin hydrochloride in combined dosage form. Every solifinacin succinate and tamsulosin hydrochloride was scanned in the wavelength region of 200-400 nm for determination of sampling wavelengths and selected sampling wavelengths were selected. Sampling wavelengths were chosen at 265 nm (zero crossing of solifinacin succinate) where the absorbance of tamsulosin hydrochloride was important and at 250 nm (zero crossing of tamsulosin hydrochloride) where the absorbance of solifinacin succinate was significant. For solifenacin succinate, linearity ranged from 10 to 100 μg/ml with a correlation coefficient of 0.998 and 2 to 10 μg/ml for the correlation coefficient of tamsulosin hydrochloride is 0.9988. The median recovery was considered to be satisfactory. For the routine study of solifenacin succinate and tamsulosin hydrochloride in combined dosage forms, the approach proposed can be applied.

Development and Validation of a Stability-Indicating HPLC Method for Empagliflozin and Linagliptin in Tablet Dosage Form

A simple, stability indicating high performance liquid chromatographical (HPLC) method was developed and validated for the estimation of empagliflozin and linagliptin in combined dosage forms. Chromatographical separation was optimized by isocratic HPLC using C-18 column [BDS 250 mm × 4.6 mm, 5 μm] utilizing a mobile phase consisting a mixuture of 0.1% orthophosphoric acid and acetonitrile (60:40 v/v) running at a rate of 1 mL/min and monitoring effluents at 230 nm. The retention time of empagliflozin and linagliptin was 2.05 min and 4.10 min, respectively. Correlation coefficient (r2) was 0.999 for both empagliflozin and linagliptin. The precision of method for the analysis of empagliflozin and linagliptin were 0.33 and 0.22, respectively. The accuracy of method (as recovery) was 100.96 to 101.48% for empagliflozin and 100.09 to101.13% for linagliptin. The results indicate the present method is accurate, precision and rugged as these results are within the specified limits. Therefore, the validated economical methodology can be applied for forced degradation study of empagliflozin and linagliptin in solid dosage forms.

Development and Validation of UV Spectroscopic and RP- HPLC Method for Determination of Levetiracetam in Bulk and Combined Dosage Form

Development and Validation of UV Spectroscopic and RP- HPLC Method for Determination of Levetiracetam in Bulk and Combined Dosage Form

Simultaneous Spectrophotometric Estimation of Emtricitabine and Tenofovir disoproxil fumarate by Area Under Curve Method in Combined Dosage Form

Simultaneous Spectrophotometric Estimation of Emtricitabine and Tenofovir disoproxil fumarate by Area Under Curve Method in Combined Dosage Form

Method development and validation of spectrophotometric and RP-HPLC methods for simultaneous estimation of spironolactone and furosemide in bulk and combined tablet dosage forms

Method development and validation of spectrophotometric and RP-HPLC methods for simultaneous estimation of spironolactone and furosemide in bulk and combined tablet dosage forms

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.