Drotaverine HCl Research Articles

Smart green spectrophotometric assay of the ternary mixture of drotaverine, caffeine and paracetamol in their pharmaceutical dosage form

Three green and facile spectrophotometric methods were developed for the assay of Petro® components; drotaverine HCl (DRT), caffeine (CAFF), and paracetamol (PAR). The three methods depend on measuring the absorbance of the studied drugs through their ethanolic solution. The first derivative spectrophotometry (FDS) at (Δλ = 10) were good parameters for DRT and CAFF resolution; DRT and CAFF could be well calibrated using FDS at 320 and 285 nm, respectively. PAR could be estimated at 308 nm utilizing the second derivative spectrophotometry (SDS). Method II relies on the double divisor ratio derivative spectroscopy (DDRDS). The first derivative was applied on each drug where they would be assayed at 309, 288, and 255 nm for DRT, CAFF, and PAR, respectively. Method III depends on the mean centering (MCR) technique. DRT, CAFF, and PAR could be determined at 309, 214, and 248 nm, respectively. The concentrations were rectilinear in the ranges of 2–20 µg/mL for DRT, 1.5–15 µg/mL for CAFF, and 2–40 µg/mL for PAR in double devisor and mean centering but PAR from 5 to 40 µg/mL in derivative method. Method validation was performed according to ICH guidelines assured by the agreement with the comparison method. In addition, greenness assessment of the proposed methods was investigated. The application of the proposed method was extended to analyse tablet dosage form and performing invitro dissolution testing.

Smart chemometrics-assisted spectrophotometric methods for efficient resolution and simultaneous determination of paracetamol, caffeine, drotaverine HCl along with three of their corresponding related impurities

Three novel, simple and accurate multivariate spectrophotometric assisted mathematical techniques were developed for determination of paracetamol, caffeine, drotaverine HCl and their related impurities. The used multivariate algorithms are principal component regression (PCR), partial least squares (PLS), and synergy intervals partial least squares (siPLS). Linearity of the suggested methods was found to be (1.00–14.60, 1.40–7.00, 1.40–3.80, 1.00–3.00, 1.50–3.50 and 2.50–4.50 µg/mL) for paracetamol, caffeine, drotaverine HCl, and their related impurities; p-aminophenol, theophylline and homoveratric acid, correspondingly. The presented methods were effectively implemented in the determination of the cited compounds in their laboratory prepared mixtures. Commercially available tablet preparation was also analyzed using the applied methods where no impurities were detected and without interference from tablet additives. Moreover, statistical analysis did not reveal any noticeable differences between the obtained results and those acquired from the reported method in terms of accuracy and precision. The developed multivariate algorithms were validated by means of internal and external validation sets. The obtained results showed the siPLS algorithm’s superiority to PCR and PLS according to the values of correlation coefficient values (r) and the lowest root mean square error of prediction (RMSEP). The combination of four subintervals [10, 12, 14, and 17] produced the highest efficiency model. Furthermore, these methods may be an applicable substitute to HPLC ones in quality control laboratories during rush of analyses where several samples have to be analyzed in a short time.

Smart Chemometrics- Assisted Spectrophotometric Methods for Efficient Resolution and Simultaneous Determination of Paracetamol, Caffeine, Drotaverine Hcl and Their Corresponding Related Impurities

Smart Chemometrics- Assisted Spectrophotometric Methods for Efficient Resolution and Simultaneous Determination of Paracetamol, Caffeine, Drotaverine Hcl and Their Corresponding Related Impurities

Development and Evaluation of Floating Sustained Release Bilayer Tablets Containing Drotaverine HCl

Development and Evaluation of Floating Sustained Release Bilayer Tablets Containing Drotaverine HCl

A reversed-phase-high performance liquid chromatography method for simultaneous determination of paracetamol, caffeine, drotaverine HCl and their related impurities with dissolution profiling of their tablets and greenness profile assessment.

A sensitive, specific and eco-friendly reversed-phase-HPLC method was developed and validated for the determination of paracetamol, caffeine and drotaverine HCl along with their related impurities. The separation was accomplished using an X-bridge C18 column (5 μm; 250 mm × 4.6 mm inner diameter) and a green mobile phase consisting of methanol and 0.02 M phosphate buffer at pH 5.0 in the gradient elution mode. The detector used was a diode array detector. The proposed method was validated in accordance with the International Conference on Harmonisation guidelines. Linear regressions were found in the range of 1-100, 1-100, 2-60, 1-20, 0.50-30 and 1-15 μg/mL for paracetamol, caffeine, drotaverine HCl, p-aminophenol, theophylline and 3,4-dimethoxyphenylacetic acid, respectively. The suggested method was successfully applied for the determination of the studied drugs in their tablet dosage form without interference from any excipients. No discernible difference was found between the obtained results and official or reported methods, statistically, in terms of both accuracy and precision. Dissolution profiling of the studied tablet was also performed using the suggested procedure. Moreover, the greenness profile was assessed using three different tools, namely, the National Environmental Methods Index, the Analytical Eco-Scale and the Analytical GREEnness Metric Approach. The acquired results assert the agreement of the assay with green chemistry principles.

Formulation, Optimization and Evaluation of Drotaverine HCl Mini Tablet

The aim of present research was to develop a mini tablet of Drotaverine hydrocholoride. Mini tablets of Drotaverine hcl were prepared by using various polymers, such as gellan gum and carbopol 940. Mini tablets were evaluated for weight variation, hardness, thickness, friability, drug content, and in-vitro dissolution studies. The prepared mini tablets exhibited satisfactory physic-chemical characteristics. All prepared batches shown good in-vitro dissolution studies. The best result from optimized batches is of F5 which gives drug release 97.72% in 12 h time periods.

Utility of micellar liquid chromatography as an analytical tool for the estimation of three binary antibiotic mixtures. Application to biological fluids

A reliable and sensitive micelle based liquid chromatography (MLC) was developed aiming to simultaneously estimate three binary antibiotic mixtures namely: cefixime (CFX) in combination with either linezolid (LNZ) (mixture Ι) or levofloxacin hemihydrate (LEV) (mixture II), and nifuroxazide (NX) with drotaverine HCl (DV) (mixture IΙI). All mixtures were separated using a micellar mobile phase prepared in 0.02 M phosphoric acid and consisting of an anionic surfactant; sodium dodecyl sulphate, triethylamine (0.3%), n-propanol, adjusted to pH 2.5 (for mixtures Ι and ΙΙ) or pH 5 for mixture ΙΙΙ with detection wavelengths of 254, 295, and 210 nm for the three mixtures respectively. Separation of the first two mixtures was conducted using a C18 column, while the last mixture was separated using a C18 monolithic column. Drugs in mixture I were rectilinear at (1.0–320.0 µg/mL) and (0.5–320.0 µg/mL) for CFX and LNZ, respectively with corresponding detection limits of 0.3269 and 0.0512 µg/mL and quantitation limits of 0.9906 and 0.1552 µg/mL, while pharmaceutical agents in mixture II showed linearity over the ranges of (0.125–80.0 µg/mL) and (0.25–160.0 µg/mL) for CFX and LEV, respectively with corresponding detection limits of 0.0154 and 0.026 µg/mL and quantitation limits of 0.0465 and 0.0789 µg/mL. Whereas linearity ranges of the analytes in mixture ΙΙΙ were 0.5–400.0 µg/mL and 2.0–400.0 µg/mL for NX and DV respectively with corresponding detection limits of 0.1822 and 0.2631 µg/mL and quantitation limits of 0.5522 and 0.7974 µg/mL. The proposed method was thoroughly validated; besides it was applied to estimate the concerned analytes in their dosage forms. The results obtained from the developed method and the reference methods were in accordance. The proposed method was further extended to determine drugs of mixtures Ι and ΙΙ in spiked human plasma without any extraction steps with high recovery percentages.

PREPARATION AND EVALUATION OF DROTAVERINE HCL ORAL DISINTEGRATING TABLETS USING SOLID MIXTURE TECHNIQUE

Objective: The objective of this study is to formulate orally disintegrating taste masked tablets of drotaverine HCl using solid mixture technique.Methods: Taste masked drug-polymer solid mixtures of drotaverine HCl were prepared by using hydroxypropyl methylcellulose (HPMC) 3 cps and rxcipient® FM1000/calcium silicate (rxcipient) as carriers employing kneading method using varying drug-polymer ratios of 1:1, 1:5, 1:7.5, and 1:9. Prepared drug-polymer mixtures evaluated for taste masking, and the ratio of drug-polymer is optimized. The granules and tablets prepared with optimized drug-polymer ratio were evaluated for pre- and post-compression parameters, in vitro dissolution studies, Fourier-transformation infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD) studies.Results: The drug:polymer ratios 1:7.5 with rxcipient and 1:9 with HPMC were optimized based on taste evaluation. The pre-compression results showed that all the formulae have good flow properties. The post-compression evaluations showed that all the formulae met the specifications of orally disintegrating tablets. From all the prepared taste masked drotaverine HCl tablets, R10 formulation consisting of 4% croscarmellose sodium and H9 formulation consisting of 3% croscarmellose sodium, 3% sodium starch glycolate, and 2% microcrystalline cellulose shown more than 99% drug release in 60 min, and both the formulations showed better taste masking and were meting oral disintegrating tablet (ODT) parameters. The optimized formulation was characterized by FTIR, DSC, and XRD studies and found no incompatibility.Conclusion: The results demonstrated that the prepared drotaverine HCl ODT showed better taste masking and meeting the parameters of ODT formulations R10 and H9. The present solid mixture technique can be effectively used for taste masking.

Determination of residues of acetaminophen, caffeine, and drotaverine hydrochloride on swabs collected from pharmaceutical manufacturing equipment using HPLC in support of cleaning validation.

An HPLC method was developed for the simultaneous determination of residues of acetaminophen (paracetamol, PA), caffeine (CA), and drotaverine HCl (DH) on swabs collected from pharmaceutical manufacturing equipment surfaces. The challenge in cleaning validation is to develop analytical methods that are sensitive enough to detect traces of the active compounds remaining on the surface of pharmaceutical manufacturing equipment after cleaning. Chromatography was performed in the isocratic mode on a Hypersil C18 BDS column using the mobile phase 0.02 M tetrabutylammonium bisulfate-methanol (100 + 45, v/v) at 50°C with UV detection at 210 nm. The method was tested for specificity, linearity, LOD, LOQ, accuracy, and precision for determination of traces of the above-mentioned drugs. The time required for a single analysis was 12 min. The response was linear in the ranges of 6.900-52.100, 1.040-7.800, and 0.694-5.210 μg/mL for PA, CA, and DH, respectively.

English

To develop a simple and sensitive method for the simultaneous estimation of drotaverine HCL (DRH) and aceclofenac (AF) using RP-HPLC. The HPLC separation was achieved on a thermo column (250 mm × 4.6 mm, 5μ) with an isocratic mixture of acetonitrile and 5 mM of ammonium acetate in the ratio of 65:35, pH adjusted to 4.5 at a flow rate of 1.0 ml/min and the detection at 285nm. The method was validated as per ICH guidelines. The retention time for DRH and AF was 3.9 and 5.0 minutes, respectively. The optimized method was linear in the range of 50 - 120 ng/ml and 100 - 700 ng/ml for DRH and AF respectively. The overall recovery of DRH and AF were 99.8 and 99.5 % respectively. The developed sensitive, robust and rugged method as proven reproducibility of the result obtained as an outcome of small deliberate variation in the analytical parameter and the change the operator.

Analytical Method Devlopment and Validation for Estimation of Drotaverin Hcl in Bulk and Tablet Formulation

The present study was aimed to develop and validates for the analysis of Drotaverine HCl in bulk and tablet formulation. Drotaverine HCl in presence of acidic medium reacts with excess amount of potassium bromide bromate with crystal violet and oxidizes crystal violet. It shows the absorbance at 590nm.The Beer’s law was obeyed in the concentration of 10-60mcg/ml. The method was validated for linearity, accuracy, precision and ruggedness. Proposed method was Statistically validated by recovery studies.

SIMULTANEOUS DETERMINATION OF PARACETAMOL, CAFFEINE, DOMPERIDONE, ERGOTAMINE TARTRATE, PROPYPHENAZONE, AND DROTAVERINE HCL BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

A high performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of paracetamol, (acetaminophen), caffeine, domperidone, ergotamine tartrate, propyphenazone, and drotaverine HCl. The chromatography was performed in the isocratic mode on a Hypersil C18 BDS column using a mobile phase consisting of 0.02 mole L−1 tetrabutylammonium bisulphate and methanol (100:45, v/v) at 50°C using UV detection at 210 nm. The method was validated by specificity, linearity, limit of detection, and limit of quantification, accuracy, and precision for the aforementioned drugs. The time required for a single analysis amounts to 14 min. The response was linear for the drug concentration ranges of 6.20–420.00, 0.80–80.00, 0.80–64.00, 2–40.00, 1.20–240.00, and 3.20–64.00, µg mL−1 for PA, CA, DO, ET, PP, and DH, respectively. Accuracy values for the method ranged from 99.40–101.94, 98.48–101.13, 98.97–100.54, 96.47–102.43, 98.92–101.82, and 97.63–100.45% for PA, CA, DO, ET, PP, and DH, respectively.

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF DROTAVERINE HCl AND NIMESULIDE FROM TABLET DOSAGE FORM

A new simple, specific, precise and accurate reversed-phase liquid chromatography method has been developed for simultaneous estimation of Drotaverine HCl (DRO) and Nimesulide (NIM) in tablet formulation. The separation was achieved on a 5-micron C18 column (250 X 4.6 mm) using mobile phase consisting of a mixture of water: acetonitrile: methanol 30: 35: 35 % (pH 2.5, adjusted with orthophosphoric acid). The flow rate was maintained at 1.0 ml/min, with an average operating pressure of 2630 psi. The detection of the constituents was done using UV detector at 295 nm for DRO and NIM. The retention time of DRO and NIM were approximately 5.6 and 10.6 min respectively. Recovery study values of DRO and NIM is 100.06+ 0.40 and 100.13+ 0.34 respectively, relative standard deviation of less than 2% for the assay show that the method is precise, accurate and linear in the concentration given and demonstrate the method developed is rugged and robust. Linear response obtained for DRO was in the concentration range 50-250

Spectrofluorometric Determination of Drotaverine Hydrochloride in Pharmaceutical Preparations

A highly sensitive, spectrofluorometric method was developed for the determination of drotaverine HCl in pharmaceutical preparations. The proposed method is based on the measurement of the native fluorescence of the drug in 0.1 M H2SO4 at emission 465 nm after excitation at 295 nm. The relative fluorescence intensity-concentration plot was rectilinear over the range of 0.16–4 µg·ml−1, with good correlation (r = 0.9999) and a lower limit of detection (LOD) of 0.032 µg·ml−1. The proposed method was successfully applied for the determination of drotaverine HCl in tablets and ampoules with a recovery percentage of 100.42 ± 0.601,99.83 ± 0.82 and 99.43 ± 1.08, respectively, which were in accordance with those obtained by a compendial method.

Quantitative estimation of benzylisoquinoline derivatives by coulometric titration

A method for estimating papaverine HCl and drotaverine HCl by coulometric titration with biamperometric indication of the end point was developed. The stoichiometric coefficients of the reactions of papaverine and drotaverine with electrogenerated chlorine were determined. Microgram quantities of agents in substance and therapeutic forms were estimated with a relative standard deviation (RSD) of 0.01–0.03.

Spectrophotometric determination of pipazethate HCl, dextromethorphan HBr and drotaverine HCl in their pharmaceutical preparations

A simple, accurate and highly sensitive spectrophotometric method is proposed for the rapid determination of pipazethate hydrochloride, dextromethorphan hydrobromide and drotaverine hydrochloride using chromotrope 2B (C2B) and chromotrope 2R (C2R). The method consists of extracting the formed ion-associates into chloroform in the case of pipazethate HCl and dextromethorphan HBr or into methylene chloride in the case of drotaverine HCl. The ion-associates exhibit absorption maxima at 528, 540 and 532 nm with C2B and at 526, 517 and 522 nm with C2R for pipazethate HCl, dextromethorphan HBr and drotaverine HCl, respectively. The calibration curves resulting from the measurements of absorbance–concentration relations (at the optimum reaction conditions) of the extracted ion-pairs are linear over the concentration range 4.36–52.32 μg mL −1 for pipazethate, 3.7–48.15 μg mL −1 for dextromethorphan and 4.34–60.76 μg mL −1 for drotaverine, respectively. The effect of acidity, reagent concentration, time, solvent and stoichiometric ratio of the ion-associates were estimated. The molar absorptivity and Sandell sensitivity of the reaction products were calculated. Statistical treatment of the results reflects that the procedure is precise, accurate and easily applied for the determination of the drugs under investigation in pure form and in their pharmaceutical preparations.

Spectrophotometric and spectrodensitometric determination of paracetamol and drotaverine HCl in combination

Thin-layer chromatography, first derivative, ratio spectra derivative spectrophotometry and Vierordt's method have been developed for the simultaneous determination of paracetamol and drotaverine HCl. TLC densitometric method depends on the difference in Rf values using ethyl acetate:methanol:ammonia (100:1:5 v/v/v) as a mobile phase. The spots of the two drugs were scanned at 249 and 308 nm over concentration ranges of 60–1200 μg/ml and 20–400 μg/ml with mean percentage recovery 100.11% ± 1.91 and 100.15% ± 1.87, respectively. The first derivative spectrophotometric method deals with the measurements at zero-crossing points 259 and 325 nm with mean percentage recovery 99.25% ± 1.08 and 99.45% ± 1.14, respectively. The ratio spectra first derivative technique was used at 246 and 305 nm with mean percentage recovery 99.75% ± 1.93 and 99.08% ± 1.22, respectively. Beer's law for first derivative and ratio spectra derivative methods was obeyed in the concentration range 0.8–12.8 and 0.4–6.4 μg/ml of paracetamol and drotaverine HCl, respectively. Vierordt's method was applied to over come the overlapping of paracetamol and drotaverine HCl in zero-order spectra in concentration range 2–26 and 2–40 μg/ml respectively. The suggested methods were successfully applied for the analysis of the two drugs in laboratory prepared mixtures and their pharmaceutical formulation. The validity of the methods was assessed by applying the standard addition technique. The obtained results were statistically agreed with those obtained by the reported method.

A Comparative Study on Various Spectrometries with Thin Layer Chromatography for Simultaneous Analysis of Drotaverine and Nifuroxazide in Capsules

Three spectrophotometric methods including Vierordt's method, derivative, ratio spectra derivative, and thin layer chromatography (TLC)-UV densitometric method were developed for simultaneous determination of drotaverine HCl (DRT) and nifuroxazide (NIF) in presence of its impurity, 4-hydroxybenzohydrazide (4-HBH). In Vierordt's method, (E(1 cm)(1%)) values were calculated at 227 and 368 nm in the zero-order spectra of DRT and NIF. By derivative spectrophotometry, the zero-crossing method, drotaverine HCl was determined using the second derivative at 245 nm and the third derivative at 238 nm, while nifuroxazide was determined using the first derivative at 399 nm and the second derivative at 411 nm. The ratio spectra derivative spectrophotometry is based on the measure of the amplitude at 459 nm for DRT and at 416 nm for NIF in the first derivative of the ratio spectra. Calibration graphs of the three spectrophotometric methods were plotted in the range 1-10 microg/ml of DRT and 2-20 microg/ml of NIF. TLC-UV densitometric method was achieved on silica gel plates using ethyl acetate : methanol : ammonia 33% (10 : 1 : 0.1 v/v/v) as the mobile phase. The Rf values were 0.74, 0.50, 0.30+/-0.01 for DRT, NIF and 4-HBH, respectively. On the fluorescent plates, the spots were located by fluorescence quenching and the densitometrical area were measured at 308 and 287 nm with linear range 0.2-4 microg/spot and 0.6-12 microg/spot for DRT and NIF, respectively. The proposed methods have been successfully applied to the commercial pharmaceutical formulation without any interference of excipients. Mean recoveries, relative standard deviations and the results of the proposed methods were compared with those obtained by applying the alternate methods.