Development and validation of spectrophotometric methods for carbapenems in pharmaceutical dosage forms

Simple and sensitive spectrophotometric methods have been developed for the determination of meropenem (MRPM) and doripenem (DRPM). These methods are based on the reduction of Fe(III) into Fe(II) by the drugs and their subsequent prussian blue color formation (λ_max 720 nm) with hexacyanoferrate (III), red color formation (λ_max 510 nm) with 1,10-phenanthroline and red color formation (λ_max 520 nm) with 2,2′-bipyridyl in the methods A, B, and C, respectively. Regression analysis of Beer’s plots showed good correlation for MRPM and DRPM in the concentration range (μg/mL) 0.5–6, 2–10; 2–10, 2–14, and 2–18, 1–8 for the methods A, B, and C, respectively.     

Determination of nimesulide in pharmaceutical dosage forms by second order derivative UV spectrophotometry

In this study, nimesulide which has been used as an analgesic, antipyretic and anti-inflammatory agent, was analyzed by using second order derivative UV spectrophotometry. The solvent, the degree of derivation, ranges of wavelength and n-value were chosen in order to optimize the conditions. The concentration of nimesulide in its solutions in ethanol and chloroform were determined between the wavelength ranges of 200 and 500 nm (n = 6, delta lambda = 21) and in the linearity ranges of 2.0-90.0 microg ml(-1) in ethanol and 2.0-50.0 microg ml(-1) in chloroform by using the values obtained from the second derivative UV spectrum of the substance. The developed second derivative UV spectrophotometric method was applied to the pharmaceutical preparations such as tablet, sachet (granule) and suspension. Tablet and sachet were analysed in ethanol while the suspension was analysed in chloroform. The results obtained from derivative UV spectrophotometry were compared with those obtained by using HPLC. It was found that the difference was not statistically important between these methods. It was concluded that developed derivative UV spectrophotometric method was accurate, sensitive, precise, reproducible and could be applied directly and easily to the pharmaceutical preparations.     

Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms

A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (¹D) 251 nm and (²D) 239 nm and tretinoin at (¹D) 364 nm and (²D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60–1200 and 1.25–25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CV<3.81%, error<3.20%). Good agreement between the found and added concentrations indicates successful application of the proposed method for simultaneous determination of clindamycin and tretinoin in synthetic mixtures and pharmaceutical dosage form.     

Analysis of some antifungal drugs by spectrophotometric and spectrofluorimetric methods in different pharmaceutical dosage forms

Simple spectrophotometric and spectrofluorimetric methods are suggested for the determination of antifungal drugs; clotrimazole, econazole nitrate, ketoconazole, miconazole and tolnaftate. Spectrophotometric one depends on the interaction between imidazole antifungal drugs as n-electron donor with the pi acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in methanol or with p-chloranilic acid (p-CA) in acetonitrile. The produced chromogens obey Beer's law at lambda(max) 460, and 520 nm in the concentration range 22.5-200 and 7.9-280 microg ml(-1) for DDQ, and p-CA, respectively. Spectrofluorimetric method is based on the measurement of the native fluorescence of ketoconazole at 375 nm with excitation at 288 nm and or the induced fluorescence after alkaline hydrolysis of tolnaftate with 5 M NaOH solution at 420 nm with excitation at 344 nm. Fluorescence intensity versus concentration is linear for ketoconazole at 49.7-800 ng ml(-1) while for tolnaftate, it is in the range of 20.4-400 ng ml(-1). The proposed methods were applied successfully for the determination of all the studied drugs in their pharmaceutical formulations.     

Quantitative dexamethasone and dexamethasone sodium phosphate determinations in pharmaceutical dosage forms by high-pressure liquid chromatography.

A high-pressure liquid chromatographic procedure for quantitative dexamethasone and dexamethasone sodium phosphate determinations in all types of commercially available pharmaceutical dosage forms was developed. The method also separates dexamethasone from its phosphate salt and separates dexamethasone or its salt from a number of inactive ingredients such as benzoic acid, benzyl alcohol, some colors, creatinine, and parabens. Inactive ingredient concentrations may be estimated without additional cost. Part of the parabens present in the commercial injections may be adsorbed by the rubber closures.     

Second-order derivative spectrophotometric assay for imipramine hydrochloride and diazepam in pure admixtures and in dosage forms

The determination of imipramine HCl and diazepam in tablets by derivative spectrophotometry is described. The drugs in combined preparations have been quantified using the second-order derivative spectra of their solutions in 0.1 M HCl. The method has been applied to pure drug mixtures as well as commerical preparations and was found to be precise and reproducible. Compliance of Beer's Law was observed in the concentration range of 10–70 μg ml⁻¹ for imipramine HC1 and 2–8 μg ml⁻¹ for diazepam. Lower limits of detection at the 95% confidence level were 1.96 μg ml⁻¹ for imipramine HCl and 0.21 μg ml⁻¹ for diazepam.     

Simple spectrophotometric determination of cinnarizine in its dosage forms

A direct, extraction-free spectrophotometric method has been developed for the determination of cinnarizine in pharmaceutical preparations. The method is based on ion-pair formation between the drug and three acidic (sulphonphthalein) dyes; namely bromocresol green (BCG), bromocresol purple (BCP) and bromophenol blue (BPB) which induces an instantaneous bathochromic shift of the maximum in the drug spectrum. Conformity to Beer's law enabled the assay of dosage forms of the drug. Compared with a reference method, the results obtained were of equal accuracy and precision. A more detailed investigation of the cinnarizine-BCG ion pair complex was made with respect to its composition, association constant and free energy change. In addition, this method was also found to be specific for the analysis of cinnarizine in the presence of some of the co-formulated drugs, such as pyridoxine hydrochloride and digoxin.     

Voltammetric assay of azithromycin in pharmaceutical dosage forms

The oxidative behaviour of azithromycin was studied at s glassy carbon electrode in different buffer system using cyclic, linear sweep and differential pulse voltammetry. The oxidation process was shown to be irreversible over the entire pH range studied (5-11) and was diffusion-adsorption controlled. Analytical method with adequate precision and accuracy was developed for the determination of azithromycin in phosphate buffer at pH 7 as supporting electrolyte containing 10% methanol and 0.05 M ammonium acetate. The peak current varied linearly with azithromycin concentration in the range 1-15 microg/ml. The procedure was successfully applied for assay of the drug in the pharmaceutical dosage forms. The relative standard deviation (n = 5) of 2.18% was obtained.     

药物制剂开发

近年来,全球前50强制药公司均已将药物制剂开发广泛融入产品生命周期管理策略。据统计,2002-2005年所有上市的产品中有39%是通过制剂改进才将产品推上市场的。1瞄准战略高地释药系统是创造畅销药品的重要保障之一(见表1)。1986年,我国首次将制剂研究课题列为“七五”国家科技攻     

Polarographic determination of EDTA in certain pharmaceutical dosage forms

A highly sensitive polarographic method was developed for the determination of EDTA added as a preservative in certain pharmaceutical preparations. The method involved chelation with Eu(III) followed by polarographic measurement of the chelate formed. A well-defined cathodic wave was developed in Britton–Robinson buffers over the pH range 2–12. The wave was characterized as being quasi-reversible and diffusion controlled. The current–concentration relationship was found to be rectilinear over the ranges 8–160 and 2–120 μg ml⁻¹, using DCt and DPP modes, respectively, with limit of detection of 0.1 μg ml⁻¹ using the DDP technique. The mechanism of the electrode reaction was verified. The proposed method was applied for the determination of EDTA in certain pharmaceutical dosage forms, and the results obtained were in agreement with those obtained by a reference method.     

HPTLC determination of nimesulide from pharmaceutical dosage forms

A simple, rapid, reproducible and stability indicating high performance thin-layer chromatographic method for the analysis of Nimesulide both the bulk drug and from pharmaceutical formulations is reported. The mobile phase selected consists of Cyclohexane-Ethylacetate [60:40, v/v]. It gave compact spots both for Nimesulide and its degraded products at Rf values 0.44 and 0.712, respectively. Densitometric analysis of nimesulide was carried out at 295 nm. The calibration curve of Nimesulide in methanol was linear in the range of 100-900 ng. The mean value of correlation coefficient, slope and intercept were 0.9989+/-0.0011, 504.655+/-0.0013 and 85331.56+/-0.0253, respectively. The limits of detection and quantitation were 60 and 100 ng, respectively. The drug content was within the limits (+/-5% of the labelled content of the formulations). The recovery of Nimesulide was about 99.5%.     

Kinetic spectrophotometric determination of ampicillin and amoxicillin in dosage forms

A kinetic spectrophotometric method has been developed for the determination of ampicillin (I) and amoxicillin (II). The method involves hydrolysis of the antibiotics with 1.0 M HCl, neutralization with 1.0 M NaOH followed by addition of palladium(II) chloride in the presence of 2 M KCl. The produced yellow colour is measured at 335 nm. The proposed method is valid over the concentration range 8-40 microg/ml and 10-40 microg/ml for I and II respectively with minimum detectability of 0.73 microg/ml and 0.76 microg/ml for I and II respectively. The determination of the studied compounds adopting the fixed concentration method is feasible with the calibration equations obtained, but the fixed time method has been found to be more applicable. The proposed method was applied to commercial dosage forms and the results obtained were in good agreement with those given by USP method.