Determination of meloxicam in bulk and pharmaceutical formulations

Three sensitive and reproducible methods for quantitative determination of meloxicam (mel) in pure form and in pharmaceutical formulations are presented. The first method is high performance liquid chromatography by which the drug is determined in the presence of its degradation products over concentration range 100–500 μg ml⁻¹ with mean percentage accuracy 100.13±0.53. The second method is based on measuring the absorbance of the formed neutral complex between basic methylene blue and mel in phosphate buffer (pH 8) at λ=653.5 nm over concentration range 1–5 μg ml⁻¹ with mean percentage accuracy 99.12±1.18. The third method is based on reaction between 2,3-dichloro-5,6-dicyano-p-benzoquinone resulting in the formation of an intense orange red coloured product after heating in a boiling water bath for 5 min. The coloured product exhibits an absorption maximum at 455 nm, over concentration range 40–160 μg ml⁻¹ with mean percentage accuracy 100.53±1.04.     

Determination of pioglitazone hydrochloride in bulk and pharmaceutical formulations by HPLC and MEKC methods

High Performance Liquid Chromatographic (HPLC) and Micellar Electrokinetic Chromatographic (MEKC) methods have been developed for the determination of pioglitazone, a new englycemic antidiabetic agent. Pioglitazone and its unsaturated impurity were separated by MEKC in less than 7 min using a 43 cm x 50 microm i.d. uncoated fused-silica capillary with extended light path for better sensitivity (25 kV at 30 degrees C) and a background electrolyte (BGE) consisting of 20% acetonitrile (v/v) in 20 mM sodium borate buffer pH 9.3 containing 50 mM sodium dodecyl sulphate (SDS). The influence of various parameters on the separation such as pH of the buffer, SDS concentration, buffer concentration, organic modifiers, temperature and voltage were investigated. The MEKC method was compared with HPLC method using a 5 microm symmetry C18 column (250 x 4.6 mm i.d.) eluted with a mobile phase consisting of a mixture of 50% (v/v) acetonitrile and 10 mM potassium dihydrogen phosphate buffer, adjusting the pH to 6.0 with 0.1 M KOH. The HPLC method is capable of detecting all process related compounds, which may be present at trace levels in finished products. Both methods were fully validated and a comparison was made. The results confirm that the methods are highly suitable for its intended purpose.     

LC determination of rofecoxib in bulk and pharmaceutical formulations

An isocratic reversed phase-liquid chromatographic (RP-LC) method has been developed for the determination and purity evaluation of rofecoxib in bulk and pharmaceutical dosage forms using photodiode array detection set at 225 nm. The method is simple, rapid and selective. The method is capable of detecting all process intermediates and other related compounds, which may be present at trace levels in finished products. Hence the method is very useful for process monitoring during the production of rofecoxib. Chlorophenyl methyl sulphone has been used as internal standard for the quantitative determination of rofecoxib. The method is linear in the range of 125-500 microg. The precision for inter- and intra-day assay variation of rofecoxib is below 1.6% relative standard deviation (R.S.D.). The accuracy determined as relative mean error (R.M.E.) for the intra-day assay is within +/-2.0%. The drug was extracted from tablets (Vioxx) using acetonitrile. The percentage recoveries from dosage forms were ranged from 98.2 to 102.6.     

Determination of iodochlorhydroxyquin and corticosteroids in pharmaceutical formulations.

Iodochlorhydroxyquin was separated from various corticosteroids using an acetonitrile-diatomaceous earth column. Iodochlorhydroxyquin was eluted with cyclohexane, and the corticosteroid was eluted with chloroform. Iodochlorhydroxyquin was determined by both a UV absorbance method and a new compleximetric method using the nickel chelate of iodochlorhydroxyquin. The corticosteroid was determined by the blue tetrazolium and isoniazid procedures. The average percent recovery for these four methods was 100.8, 99.4,100.7, and 99.9, respectively, for 10 known mixtures. The standard deviation for the absorbance for 10 determinations of the nickel complex was 0.002 absorbance unit (0.31%). Various characteristics of the nickel and other complexes were evaluated, including the sensitivity, solubility, and wavelength of maximum absorbance in 14 different solvents. The analyses of 23 typical products are reported, for which the standard deviation, expressed as a percentage of the amount declared, was 1.31% for the UV, 1.34% for the compleximetric, 1.49% for the blue tetrazolium, and 1.22% for the isoniazid procedures. Methods of determination in the presence of interferences are discussed.     

Spectrophotometric determination of fluoxetine hydrochloride in bulk and in pharmaceutical formulations

Two new rapid, sensitive and economical spectrophotometric methods are described for the determination of fluoxetine hydrochloride in bulk and in pharmaceutical formulations. Both methods are based on the formation of a yellow ion-pair complex due to the action of methyl orange (MO) and thymol blue (TM) on fluoxetine in acidic (pH 4.0) and basic (pH 8.0) medium, respectively. Under optimised conditions they show an absorption maxima at 433 nm (MO) and 410 nm (TB), with molar absorptivities of 2.12 x 10(-4) and 4.207 x 10(-3) l mol(-1) cm(-1) and Sandell's Sensitivities of 1.64 x 10(-2) and 0.082 microg cm(-2) per 0.001 absorbance unit for MO and TB, respectively. The colour is stable for 5 min after extraction. In both cases Beer's Law is obeyed at 1-20 microg mol(-1) with MO and 4-24 microg mol(-1) with TB. The proposal method was successfully extended to pharmaceutical preparations capsules. The results obtained by both the agreement and E.P. (3rd edition) were in good agreement and statistical comparison by Student's t-test and variance ratio F-test showed no significant difference in the three methods.     

Spectrofluorimetric analysis of certain macrolide antibiotics in bulk and pharmaceutical formulations

The macrolides (erythromycin, erythromycin esters, azithromycin dihydrate, clarithromycin and roxithromycin) can be analyzed by a simple spectrofluorimetric method based on the oxidation by cerium(VI) in the presence of sulphuric acid and monitoring the fluorescence of cerium(III) formed at λ_ex 255 nm and λ_em 348 nm. All variables affecting the reaction conditions as cerium(VI), sulphuric acid concentrations, heating time, temperature and dilution solvents were carefully studied. Linear calibration graphs were obtained in the range of 42.6–1200 ng ml⁻¹ with a percentage relative standard deviation in the range of 0.014–0.058%. Quantitation and detection limits were calculated. The method was applied successfully for the assay of the studied drugs in pure and pharmaceutical dosage forms as tablets, capsules and suspension. Recovery experiments revealed recovery of 98.3–100.8%. The effect of potential interference due to common ingredients as glucose, sucrose, lactose, citric acid, and propylene glycol was investigated. Applying standard addition method shows a recovery of 97.7–100.9% macrolide antibiotics from their corresponding dosage forms.     

Stability-indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations

A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of curcumin both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60 F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (9.25:0.75 v/v). This system was found to give compact spots for curcumin (R(f) value of 0.48 +/- 0.02). Densitometric analysis of curcumin was carried out in the absorbance mode at 430 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r = 0.996 and 0.994 with respect to peak height and peak area, respectively, in the concentration range 50-300 ng per spot. The mean value +/- S.D. of slope and intercept were 1.08 +/- 0.01, 51.93 +/- 0.54 and 8.39 +/- 0.21, 311.55 +/ -3.23 with respect to peak height and area, respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 8 and 25 ng per spot, respectively. Curcumin was subjected to acid and alkali hydrolysis, oxidation and photodegradation. The drug undergoes degradation under acidic, basic, light and oxidation conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and photo oxidation. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one.     

Determination of lignocaine and amprolium in pharmaceutical formulations using AAS.

The ion-associate complexes of lignocaine hydrochloride (Lig.Cl) with ammonium reineckate (Rk) or sodium cobaltithiocyanate, and that of amprolium hydrochloride (Amp.Cl) with ammonium reineckate, have been prepared. The precipitated ion-associates were subjected to elemental analyses, infrared and nuclear magnetic resonance spectroscopy and determination of the metal content for elucidation of their structures. The solubilities of the solid ion-associate complexes have been studied and their solubility products were determined at different temperatures at the optimum pH for their quantitative precipitation. The thermodynamic parameters DeltaH, DeltaG and DeltaS for the dissolution of the ion-associate complexes were calculated. These ion-associate complexes have been used for the quantitative determination of the above mentioned drugs by precipitating them with an excess of the inorganic metal complex ions and determining the excess metal complex ions using atomic absorption spectrometry. The method was applied for the determination of the above drugs in pure solution and pharmaceutical preparations. 0.135-135.4 and 0.158-157.6 mg of lignocaine and amprolium, respectively, can be determined with mean relative standard deviations (R.S.D.) 0.92-1.20% and recovery values of 99.18+/-0.48 to 100.12+/-0.34% indicating high precision and accuracy.     

Fluorimetric and spectrophotometric determination of ritodrine hydrochloride in bulk and pharmaceutical formulations

Two simple sensitive and accurate methods have been developed for the determination of ritodrine hydrochloride in bulk and pharmaceutical preparations. The first method involves the direct measurement of the native fluorescence of the drug in the concentration range 4-9 microg ml(-1), the second method is based on the oxidation of ritodrine HCl with cerium(IV) followed either by spectrophotometric or fluorimetric measurement in the concentration ranges 0.5-1.0 and 0.05-0.1 microg ml(-1), respectively. The interference of various formulation excipients was examined. The reliability of the proposed methods was checked at three different concentrations; the standard deviation varied from 2.7 x 10(-3)-0.109. The described methods have been applied to the determination of ritodrine HCl in tablets and ampoules. The assay results showed insignificant difference with those of the official USP 23 HPLC method.     

Stability-indicating HPTLC determination of tizanidine hydrochloride in bulk drug and pharmaceutical formulations

A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of tizanidine hydrochloride both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of toluene-acetone-ammonia (5:5:0.1, v/v/v). This system was found to give compact spots for tizanidine hydrochloride (R(f) value of 0.32+/-0.01). Tizanidine hydrochloride was subjected to acid and alkali hydrolysis, oxidation and photodegradation. Also, the degraded product was well separated from the pure drug. Densitometric analysis of tizanidine hydrochloride was carried out in the absorbance mode at 315 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9922 in the concentration range 300-1000 ng per spot. The mean value of correlation coefficient, slope and intercept were 0.9922+/-0.002, 0.064+/-0.001 and 38.09+/-1.71, respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 88 and 265 ng per spot, respectively. The drug does not undergo degradation under acidic and basic conditions. The samples degraded with hydrogen peroxide showed additional peak at R(f) value of 0.12. This indicates that the drug is susceptible to oxidation. Statistical analysis proves that the method is repeatable and selective for the estimation of said drug. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one.     

Hydrogels in pharmaceutical formulations.

The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.     

Stability indicating HPTLC determination of Trimetazidine as bulk drug and in pharmaceutical formulations

A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of trimetazidine hydrochloride both as a bulk drug and in formulations is reported. The mobile phase composition was n-butanol-water-methanol-ammonia (20%) (14:0.2:0.2:2, v/v/v/v). Densitometric analysis of trimetazidine hydrochloride was carried out in the absorbance mode at 254 nm. the calibration curve of trimetazidine hydrochloride in methanol was linear in the range 400 -- 2400 ng. The mean value of correlation coefficient, slope and intercept were 0.99815 and #61617;0.001, 0.4849 and #61617;0.001 and 31.633 and #61617;5.996 respectively. The limits of detection and quantitation were 50 and 80 ng respectively. The recovery of trimetazidine hydrochloride was about 98 -- 100%. This method was utilized to analyze trimetazidine hydrochloride from conventional tablets and controlled release pellets in the presence if commonly used excipients.     

LC determination and purity evaluation of nefazodone HCl in bulk drug and pharmaceutical formulations

A thin layer chromatographic-densitometric method for identification and quantitation of neomycin sulfate, polymixin B sulfate, zinc bacytracin and auxiliary substances (methyl and propyl hydroxybenzoates) in ophthalmic ointment was developed. To separate these constituents the silica gel coated TLC plates and two mobile phases were used. The suitable mobile phases were: methanol-n-butanol-ammonia 25%-chloroform (14:4:9:12, v/v/v/v) for determination of antibiotics and n-pentane-glacial acetic acid (66:9, v/v) for methyl and propyl hydroxybenzoates. The antibiotic chromatograms were detected by using ninhydrin ethanol solution, while densitometric measurements were made at lambda = 550 nm. Hydroxybenzoates were identified by UV measurements at lambda = 260 nm. The constituents under consideration were well separated at sufficient detection level. The recovery for all constituents ranged from 98.08% to 104.95%.     

Spectrophotometric determination of indinavir in bulk and pharmaceutical formulations using bromocresol purple and bromothymol blue

A simple, sensitive and selective method for the determination of indinavir (IND) in bulk and in pharmaceutical formulations is described. The method is based on extraction of this drug into chloroform as ion-pair with sulphonphthalein dyes as bromocresol purple (BCP) and bromothymol blue (BTB). The optimum conditions of the reactions were studied and optimized. The absorbance of the yellow products was measured at 427 nm for IND-BCP and 420 nm for IND-BTB. The calibration graphs were linear over the range 4.0-60.2 microg x ml(-1) of drug in chloroform, using the two dyes. The composition of the ion-pairs was established by the molar ratio method. For IND the molar ratio was determined to be 1:1 by measurement of first derivative signals at 273 nm. A calibration graph was established for 3.0-70.6 microg x ml(-1) of IND for first derivative spectrophotometry. The developed method was applied successfully for the determination of IND in pharmaceutical formulations. The data obtained were compared the data given by first derivative spectrophotometry. No differences were found.     

Determination of propylene carbonate in pharmaceutical formulations using liquid chromatography

A stability-indicating reversed-phase high-performance liquid chromatographic method using a refractive index detector is described for the determination of propylene carbonate in pharmaceutical formulations. Good precision and accuracy of the method was demonstrated using an aqueous formulation. This method is also applicable to an anhydrous formulation.     

Determination of Ziprasidone in pharmaceutical formulations by capillary zone electrophoresis

The atypical antipsychotic drug Ziprasidone was determined by capillary zone electrophoresis in pharmaceutical formulations. Extraction of the drug from the formulation consisted in a simple dissolution step with methanol as solvent, and enables determination of the drug without any interference from the excipients. It was found that at pH of the background electrolyte above 5 the peak of the drug exhibited a tailing, at pH 6 or higher even a disappearance of the peak in the electropherogram was observed. This behaviour was related to the concomitant reduction of the solubility of the drug in the background electrolyte upon deprotonation at higher pH. As a consequence, analyses were carried out with formate buffer, pH 3.0, and enabled run times of about 3 min. The method was validated in terms of stability, specificity, precision, accuracy, linearity, quantitation limits, and robustness, and was applied to the analysis of different commercial capsules.     

Colorimetric acetaminophen determination in pharmaceutical formulations.

Different approaches for the colorimetric determination of acetaminophen, based on its coupling with diazotized o-nitroaniline, are described. Copper(II) chelation with the coupled compound makes the method highly selective. Sensitivity is increased when the acetaminophen assay is carried out indirectly through the determination of the chelate's copper content. Optimum conditions for performing the different approaches are described. The stoichiometric balance for the reactants in the coupled compound and chelate is determined. The degree of dissociation and the instability constant are computed. The rectilinear relationship between the absorbance of the different products and the concentration of acetaminophen allows for its determination in different pharmaceutical formulations. Compared with the official method, the proposed methods give more accurate results.