Hesham Salem

Spectrophotometric determination of β-adrenergic blocking agents in pharmaceutical formulations

Simple, rapid and sensitive spectrophotometric procedures were developed for the analysis of atenolol, timolol maleate, propranolol hydrochloride, metoprolol tartarate, betaxolol hydrochloride, levobunolol hydrochloride and bisprolol fumarate in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of these drugs as n-electron donors with the sigma-acceptor iodine, and the pi-acceptors: 7,7,8,8-tetracyanoquinodimethane, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyanoethylene, 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil) and 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil). The obtained charge-transfer complexes were measured at 365 nm for iodine (in 1,2-dichloroethane), at 840, 420, and 470 nm for 7,7,8,8-tetracyan-oquinodimethane, tetracyanoethylene and 2,3-di-chloro-5,6-dicyano-1,4-benzoquinone (in acetonitrile), respectively, and at 450 and 440 nm for bromanil and chloranil (in ethanol), respectively. Due to the rapid development of colors at ambient temperature, the obtained results were used on thin-layer chromatograms for the detection of the investigated drugs. Beers plots were obeyed in a general concentration range of 4-120 microg ml(-1) with correlation coefficients not less than 0.9991. The proposed procedures could be applied successfully to the determination of the investigated drugs in tablets and ophthalmic solutions with good recovery; percent ranged from 98.03+/-0.98 to 100.30+/-0.90. The association constants and standard free energy changes using Benesi-Hildebrand plots were studied.

Colourimetric and AAS determination of cephalosporins using Reineck's salt.

Two simple, accurate, sensitive and selective procedures for the determination of eight cephalosporins are described. These procedures are based on the formation of ion-pair complexes between the drugs and ammonium reineckate, the formed precipitates are quantitatively determined either colourimetrically or by atomic absorption spectrometrically. The methods consist of reacting drugs with Reineckes salt in an acidic medium at 25+/-2 degrees. The first colourimetric procedure (procedure I) is based on dissolving the formed precipitate with acetone, the volume was completed quantitatively and the absorbance of the solution was measured at 525 nm against pure solvent blank. Also, the formed precipitates on the atomic absorption spectrometric procedure (procedure II) are quantitatively determined directly or indirectly through the chromium precipitate formed or the residual unreacted chromium in the filtrate at 358.6 nm. The optimum conditions for precipitation have been carefully studied. Beers law is obeyed for the studied drugs in the range 5-35 microg ml(-1) with correlation coefficients not less-than 0.9989. Both procedures I and II hold well accuracy and precision when applied to the analysis of the cited cephalosporins in different dosage forms with good recovery percent ranged from 98.7+/-0.90 to 100.1+/-0.74 without interference from additives.

Selective spectrophotometric determination of phenolic β-lactam antibiotics

Abstract Two simple and selective spectrophotometric methods were developed for the quantitative determination of cefoperazone sodium, cefadroxil monohydrate, cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their pharmaceutical formulations. The methods are based on the selective oxidation of these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense yellow coloured product ( λ max =397 nm). The reaction conditions were studied and optimized. Beers plots were obeyed in a general concentration range of 5–30 μg ml −1 with correlation coefficients not less than 0.9979 for the four drugs with the two reagents. The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate, flucloxacillin or dicloxacillin. They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 99.7 (±0.46) to 100.32 (±1.05) in the Ce (IV) method and 99.6 (±0.50) to 100.3 (±1.32) in the Fe (III) method. Interferences from other antibiotics and additives products were investigated.

Formulation of controlled-release baclofen matrix tablets: Influence of some hydrophilic polymers on the release rate and in vitro evaluation

This work aims at investigating different types and levels of hydrophilic matrixing agents, including methylcellulose (MC), sodium alginate (Alg), and sodium carboxymethylcellulose (CMC), in an attempt to formulate controlled-release matrix tablets containing 25 mg baclofen. The tablets were prepared by wet granulation. Prior to compression, the prepared granules were evaluated for flow and compression characteristics. In vitro, newly formulated controlled-release tablets were compared with standard commercial tablets (Lioresal and baclofen). The excipients used in this study did not alter physicochemical properties of the drug, as tested by the thermal analysis using differential scanning calorimetry. The flow and compression characteristics of the prepared granules significantly improved by virtue of granulation process. Also, the prepared matrix tablets showed good mechanical properties (hardness and friability). MC- and Alg-based tablet formulations showed high release-retarding efficiency, and good reproducibility and stability of the drug release profiles when stored for 6 months in ambient room conditions, suggesting that MC and Alg are good candidates for preparing modified-release baclofen tablet formulations.

Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation, characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed by solid state analyses. Complete drug amorphiztion was attained at 1∶3 (wt/wt) drug: PVP, 25% (wt/wt) ND in PVP. According to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris at ∼129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution efficiency, respectively. In vivo experiments in mice demonstrated that administration of 60 mg/kg of drug coprecipitated with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power, dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing a reduced-dose, fast-release solid oral dosage form of nimesulide.

Analytical Study for the Charge-Transfer Complexes of Pregabalin

Studies were carried out, for the first time, to investigate the charge-transfer reactions of Pregabalin (PRE) as n-electron donor with various π-acceptors: 7,7,8,8-tetracyanoquinodimethane (TCNQ), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone (chloranilic acid, pCA), tetracyanoethylene (TCNE) and 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil). Different colored charge-transfer complexes and radical anions were obtained. Different variables affecting the reactions were studied and optimized. The formations of the colored complexes were utilized in the development of simple, rapid and accurate spectrophotometric methods for the analysis of PRE in pure form as well as in its pharmaceutical preparation. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9995-0.9999) were found between the absorbance and the concentrations of PRE in the range of 8-400 µg mL-1. The limits of assays detection ranged from 0.60 to 8.11 µg mL-1. No interference could be observed from the additives commonly present in the capsules. The methods were successfully applied to the analysis of capsules that contain PRE, with good accuracy and precision; the recovery percentages ranged from 100.19±0.83 to 100.50±0.53. The results were compared favorably with the reported method.

Atomic Absorption Spectrometry of Flufenamic Acid

Abstract A simple and accurate method was described for the quantitative determination of flufenamic acid utilizing precipitation reactions with silver (I), copper (II) and iron (III). Flufenamic acid was precipitated from its neutral alcoholic solution by silver nitrate, copper acetate or ferric chloride standard solutions followed by direct determination of the above cited ions in the precipitate or its indirect determination in the filtrate applying atomic absorption spectroscopy. The optimum conditions for precipitation have been carefully studied. The molar ratio of the reactants were ascertained. Statistical analysis of the results obtained compared to the results of the official method revealed equal precision and accuracy. The suggested procedures were applied for determining flufenamic acid in pharmaceutical preparations as well and proved validity.

Spectrofluorimetric determination of certain biologically active phenothiazines in commercial dosage forms and human plasma.

A validated simple and sensitive spectrofluorimetric method was developed for the determination of chlorpromazine hydrochloride, promethazine hydrochloride, trifluperazine hydrochloride, thioridazine hydrochloride, perazine maleate and oxomemazine. The method was based on condensation of malonic acid/acetic anhydride (MAA) under the catalytic effect of the tertiary amine moiety of the studied phenothiazines to provide a deep yellow to brown colour with green fluorescence. Relative fluorescence intensity of the products was measured at λ exc 398 nm and λ em 432 nm. Different variables affecting the reaction were studied and optimized. The method was successfully applied for the determination of the studied drugs in commercial dosage forms. The lower detection limits allowed the application of this method for the determination of the compounds in plasma as an example of a biological fluid. In addition, the method was considered specific for the determination of tertiary amines in the presence of primary and secondary amines; as a result, it was deemed suitable for the determination of the cited drugs in the presence of their degradation products resulting from N-dealkylation or oxidation of the corresponding sulphoxides or sulphones.