Pharmaceutical Formulation

A bare graphite-polyurethane composite was evaluated as an alternative electrode in the determination of atenolol (ATN) in pharmaceutical formulations. Using a DPV procedure, a linear analytical curve was observed in the 4-100mumolL(-1) range with a LOD=3.16mumolL(-1), without need of surface renewing between successive runs, with recoveries between 95.5 and 108%. Interference of other antihypertensive drugs was observed, but not from the usual components of tablets. The results of the proposed method agreed with HPLC ones within 95% confidence level.

Sensitive and selective stability-indicating assay methods (SIAMs) are suggested for the determination of cilostazol (CIL) in the presence of its acid, alkaline and oxidative degradation products. Developing SIAMs is necessary to carry out any stability study. Stress testing of CIL was performed according to the International Conference on Harmonization (ICH) guidelines in order to validate the stability-indicating power of the analytical procedures. Stress testing showed that CIL underwent acid, alkaline and oxidative degradation; on the other hand, it showed stability towards photo-and thermal degradation. Two chromatographic SIAMs were developed, namely HPLC and HPTLC methods. The concentration range and the mean percentage recovery were 1.0-31.0 g/ml and 99.96 ± 0.46 and 0.6-14.0 g/spot and 99.88 ± 1.10 for HPLC and HPTLC methods, respectively. In addition, derivative spectrophotometric methods were developed in order to determine CIL in the presence of its acid degradation product; these were performed by using the third derivative spectra ( 3 D) and the first derivative of the ratio spectra ( 1 DD) methods. The linearity range and the mean percentage recovery were 2.0-34.0 g/ml and 100.27 ± 1.20 for the ( 3 D) method, while they were 2.0-30.0 g/ml and 99.94 ± 1.18 for the ( 1 DD) method. Also, two chemometric-assisted spectrophotometric methods, based on using partial least squares (PLS) and concentration residual augmented classical least squares method (CRACLS), for the determination of CIL were developed. Both methods were applied on zero order spectra of the mixtures of CIL and its acid degradation product, the mean percentage recovery was 100.03 ± 1.09 and 99.91 ± 1.27 for PLS and CRACLS, respectively. All methods were validated according to the International Conference on Harmonization (ICH) guidelines and applied on bulk powder and pharmaceutical formulations.

We describe the identification of novel rapamycin derivatives present as low-level impurities in active pharmaceutical ingredients using an integrated, multidisciplinary approach. Rapamycin, a fermentation-derived natural product is itself used clinically and provides the starting material for several rapamycin analog drugs, typically used in oncology. LC-MS proved a sensitive means to analyze impurity profiles in batches of rapamycin. MS fragmentation was used to gain structural insight into these impurities, usually fermentation by-products, structurally very similar to rapamycin. In cases where MS fragmentation was unable to provide unambiguous structural identification, the impurities were isolated and purified using orthogonal HPLC methods. Using the higher mass sensitivity of small-volume NMR microprobes, submilligram amounts of isolated impurities were sufficient for further characterization by multidimensional NMR spectroscopy. Full assignment of the 1 H and 13 C NMR signals revealed the structure of these impurities at an atomic level. This systematic workflow enabled the identification of several novel rapamycin congeners from active pharmaceutical ingredient without the need for large-scale isolation of impurities. For illustration, two novel rapamycin derivatives are described in this study: 12-ethyl-rapamycin and 33-ethyl-rapamycin, which exemplify previously unreported modifications on the carbon skeleton of the rapamycin macrocycle. The methodologies described here can be of wide use for identification of closely related structures found; for example as fermentation by-products, metabolites or degradants of natural product-based drugs.

We describe the identification of novel rapamycin derivatives present as low-level impurities in active pharmaceutical ingredients using an integrated, multidisciplinary approach. Rapamycin, a fermentation-derived natural product is itself used clinically and provides the starting material for several rapamycin analog drugs, typically used in oncology. LC-MS proved a sensitive means to analyze impurity profiles in batches of rapamycin. MS fragmentation was used to gain structural insight into these impurities, usually fermentation by-products, structurally very similar to rapamycin. In cases where MS fragmentation was unable to provide unambiguous structural identification, the impurities were isolated and purified using orthogonal HPLC methods. Using the higher mass sensitivity of small-volume NMR microprobes, submilligram amounts of isolated impurities were sufficient for further characterization by multidimensional NMR spectroscopy. Full assignment of the 1 H and 13 C NMR signals revealed the structure of these impurities at an atomic level. This systematic workflow enabled the identification of several novel rapamycin congeners from active pharmaceutical ingredient without the need for large-scale isolation of impurities. For illustration, two novel rapamycin derivatives are described in this study: 12-ethyl-rapamycin and 33-ethyl-rapamycin, which exemplify previously unreported modifications on the carbon skeleton of the rapamycin macrocycle. The methodologies described here can be of wide use for identification of closely related structures found; for example as fermentation by-products, metabolites or degradants of natural product-based drugs.

Patel, et al.: RP-HPLC estimation of duloxetine hydrochloride Simple, specifi c, accurate and precise method, namely, reverse phase high performance liquid chromatography was developed for estimation of duloxetine HCl in pharmaceutical formulations. For the high performance liquid chromatography method, Phenomenox C-18, 5 µm column consisting of 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.01M 5.5 pH phosphate buffer: acetonitrile (60:40 v/v) and fi nal pH adjust to 5.5±0.02 with phosphoric acid was used. The fl ow rate was 1.2 ml/min and effl uent was monitored at 231 nm. The retention time was 5.61 min. The method was validated in terms of linearity, accuracy and precision. The linearity curve was found to be linear over 0.25-4 µg/ml. The limit of detection and limit of quantifi cation were found to be 0.10 and 0.25 µg/ml respectively. The proposed method was successfully used to determine the drug content of marketed formulations.

A crystalline organic-inorganic composite exchanger, acrylamide stannic silicomolybdate was synthesized at pH 0.63. The ion exchange capacity of the material was improved from 0.40 to 1.64 meq/g in comparison to its inorganic counterpart, stannic silicomolybdate. The FTIR, XRD and thermal studies were conducted to understand the nature of the material. Distribution coefficient studies of the metal ions on this material were performed in polar solvents such as trichloroacetic acid, formic acid, acetic acid and dimethylsulfoxide to know the ion exchange behavior and selectivity for different ions. On the basis of distribution coefficient studies, several binary separations of metal ions viz. Cd 2+ -Pb 2+ , Cd 2+ -Cu 2+ , Al 3+ -Pb 2+ , Al 3+ -Cu 2+ , Zn 2+ -Pb 2+ , Zn 2+ -Cu 2+ was achieved quantitatively on acrylamide stannic silicomolybdate columns. Pb 2+ and Cu 2+ were selectively removed from synthetic mixtures containing Cu 2+ , Mg 2+ , Cd 2+ , Hg 2+ , Zn 2+ and Ba 2 and Pb 2+ , Hg 2+ , Cd 2+ , Ba 2+ , Mg 2+ and Ba 2+ respectively. The quantitative separation of Cu 2+ and Zn 2+ were also achieved on commercially available pharmaceutical formulation I-Vit.

The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo nonclinical safety assessment studies. Although there are many vehicles available that may meet physical and chemical requirements for chemical or pharmaceutical formulation, there are wide differences in species and route of administration specific to tolerances to these vehicles. In current practice, these differences are largely approached on a basis of individual experience as there is only scattered literature on individual vehicles and no comprehensive treatment or information source. This approach leads to excessive animal use and unplanned delays in testing and development. To address this need, a consulting firm and three contract research organizations conducted a rigorous data mining operation of control (vehicle) data from studies dating from 1991 to present. The results identified 65 single component vehicles used...

New spectrophotometric procedures have been established for the quantitation of piroxicam and tenoxicam. The procedures are based on the reaction between the examined drug and alizarin (I), alizarin red S (II), alizarin yellow G (III) or quinalizarin (IV) producing ion-pair complexes which can be measured at the optimum wavelength. The optimization of the reaction conditions is investigated. Beer's law is obeyed in the concentration ranges 0.05-2.40 mg ml − 1 , whereas optimum concentration as adopted from Ringbom plots was 0.12-2.25 mg ml − 1. The molar absorptivity, Sandell sensitivity, detection and quantification limits are also calculated. The correlation coefficient was ] 0.9990 (n= 10) with a relative standard deviation (R.S.D.) of 5 1.2, for ten determinations of 1.0 mg ml − 1. The methods are successfully applied to the determination of piroxicam and tenoxicam in their pharmaceutical formulations.

A highly sensitive, accurate and simple spectrophotometric method was established for determination of naproxen (NAP). The method involved ion-pair complex formation between naproxen and bromophenol blue (BPB). The colored product was measured at 432 nm. The reaction conditions were optimized. The absorbance was found to increase linearly with increase in concentration of NAP which was corroborated by correlation coefficient value. Beer's law was obeyed in the concentration range of 1-110 µg mL -1 with molar absorptivity of 9.756×10 3 L mol -1 cm -1 . The limits of detection (LOD) and quantitation (LOQ) for the proposed method are 0.292 and 0.973 µg mL -1 , respectively. Recovery of the method was carried out by standard addition method. Recovery studies and statistical data proved the accuracy, reproducibility and the precision of the proposed method. The common excipients did not interfere in this analysis. Hence the method is useful for routine estimation of naproxen in pharmaceutical formulation and human serum samples.

Immunosafety analysis of pharmaceutical surfactants is an important step in understanding the complex mechanisms by which they induce side effects in susceptible patients. This paper provides experimental evidences that polyethoxylated surfactants, Cremophor-EL and Tween-80, also known as Polysorbate-80, activate the complement system in vitro, in normal human serum and plasma. They appeared to be more efficient reactogens than their structural homolog, Tween-20. Cremophor-EL and Tween-80 promoted the generation of biologically active complement products, C3a, C5a and C5b-9. Consistently, Paclitaxel and Taxotere (Docetaxel), pharmaceuticals formulated in Cremophor-EL and Tween-80, activated the complement system in similar extent. Moreover, comparison of serum reactivity against the drug-loaded and drug-free formulations exhibited a significant linear correlation. Taken together, these results are consistent with the hypothesis that therapeutic side effects, such as acute hypersensitivity and systemic immunostimulation, caused by intravenous nanomedicines containing polyethoxylated detergents such as Cremophor-EL and Tween-80, can be attributed to complement activation-derived inflammatory mediators.

A rapid reversed-phase type HPLC method for the simultaneous separation and analysis of dand l-thyroxine (d-and l-T 4 ) and triiodothyronine (T 3 ) was developed using a quinine-derived chiral stationary phase and applied for a quantitative assay of the enantiomeric impurity of the drugs in pharmaceutical formulations of levothyroxine. The influence of operating parameters has been studied for the optimization of the separation and also in order to gain an insight into the retention mechanism. Validation of the method included linearity, precision and accuracy which revealed R.S.D. values of <3.3% for intra-assay precision and percent error ranging from −6 to +2.1% for various defined validation samples, proving satisfactory accuracy. Quantitation was performed over the range of 0.5-500 g ml −1 with limits of detection and quantitation lower than 0.1 and 0.5 g ml −1 , respectively, for both analytes. Further, the determination of 0.1% impurity, of d-T 4 as well as land d-T 3 in levothyroxine sodium tablets proved to be feasible.

 A new fluorimetric procedure for the determination of thiamine using flow injection analysis is proposed. The method is based on the derivatization reaction of the primary amine group with o-phthalaldehyde in the presence of 2-mercaptoethanol using fluorimetric detection. The calibration graph based on peak area was linear in the range 0.2–6 ng mL−1. The detection limit was close to 0.1 ng mL−1. The method was applied to the determination of the vitamin in commercial pharmaceutical preparations.

The formation of the complex between alendronate, non-chromophoric bisphosphonate drug important for the treatment of a variety of bone diseases, and iron(III) chloride in perchloric acid solution was studied. The stoichiometric ratio of alendronate to Fe(III) ions in the chromophoric complex was determined to be 1:1. The conditional stability constant was log K% ave =4.50 (SD =0.15), indicating that the Fe(III)-alendronate complex is a complex of medium stability. The optimum conditions for this reaction were ascertained and a spectrophotometric method was developed for the determination of alendronate in the concentration range 8.1-162.5 mg ml − 1 , the detection limit being 2 mg ml − 1 . The method was validated for the direct determination of alendronate in tablet dosage formulations.

A capillary electrophoretic method has been developed for the enantioselective analysis of amisulpride in pharmaceutical formulations, using ␤-cyclodextrin sulfate as the chiral selector. Several parameters, such as cyclodextrin type and concentration, buffer concentration and pH and capillary temperature were investigated for method optimisation. Baseline enantioseparation of the racemic compound was achieved in less than 10 min using a fused silica capillary (50 m i.d. and 33.0, 8.5 cm, total and effective length, respectively), filled with a background electrolyte consisting of a 10 mM citrate buffer at pH 3.5 supplemented with 0.22% (w/v) ␤-cyclodextrin sulfate at 20 • C and applying a voltage of +15 kV. Formulation analysis was carried out after analyte extraction by methanol. The method was fully validated, with good results in terms of precision, selectivity, accuracy and amount of drug found with respect to the label claim. Thus, the method seems to be suitable for the enantiomeric analysis of amisulpride in pharmaceutical formulations.

A bismuth-film electrode for use in cathodic electrochemical detection was employed in order to quantify sulfadiazine in pharmaceutical formulations. The bismuth film was deposited ex situ onto a glassy carbon substrate. Analysis of two sulfa drugs was carried out by differential-pulse voltammetry in 0.05 mol L −1 Britton-Robinson pH 4.5 solution. Sulfadiazine reduction was observed at −0.74 V vs. Ag/AgCl in one well-resolved irreversible reduction peak. The analytical curve with two slopes was obtained in the concentration range of 3.2-97.0 mol L −1 . The detection limit was 2.1 mol L −1 for concentrations of 3.2-20.0 mol L −1 (r = 0.9949) and 12.2 mol L −1 for concentrations between 20.0 and 97.0 mol L −1 (r = 0.9951). Recovery studies carried out with both sulfadiazine samples gave values from 93.6 to 109.3%. The accuracy of the results supplied by the bismuth-film electrode was compared to those obtained by the standard amperometric titration method. The relative error between them was lower than 2.0%.

A cathodically pretreated boron-doped diamond electrode was used for the simultaneous anodic determination of ascorbic acid (AA) and caffeine (CAF) by differential pulse voltammetry. Linear calibration curves (r ¼ 0.999) were obtained from 1.9 Â 10 À5 to 2.1 Â 10 À4 mol L À1 for AA and from 9.7 Â 10 À6 to 1.1 Â 10 À4 mol L À1 for CAF, with detection limits of 19 mmol L À1 and 7.0 mmol L À1 , respectively. This method was successfully applied for the determination of AA and CAF in pharmaceutical formulations, with results equal to those obtained using a HPLC reference method.

A stability indicating HPLC method for the simultaneous determination of ciprofloxacin HCl (CIP) and metronidazole (MET) in presence of ciprofloxacin acid degradation product (DEG) is presented (Method I, MI). The present study is concerned with the development and validation of an environmentally friendly method with relatively low organic composition of the mobile phase. The chromatographic separation of the two drugs was performed using Kromasil 100-5C 18 (150 mm x 4.6 mm) with UV detection at 280 nm and flow rate of 1 mLmin -1 . The mobile phase consisted of 0.5% aqueous phosphoric acid and acetonitrile (90:10 v/v) MI. In addition, another HPLC method (MII) for the separation of the same binary mixture using 0.5% aqueous phosphoric acid and acetonitrile (80:20 v/v) was presented. Retention times were 2.40, 3.10 & 22.94 min for MET, DEG and CIP, respectively, MI. On the other hand, the retention times were 2.03 and 4.00 min for MET and CIP, respectively MII. However, the relatively low organic composition of the mobile phase of 10% in MI was advantageous regarding green analytical procedure concept. Linearity, accuracy and precision were acceptable over the concentration range of 1-65 μgmL -1 for both drugs MI, and 1-80 μgmL -1 MII. The method is new, simple , sensitive and suitable for the routine quality control and dosage form assay of both drugs in the presence of the acid degradation product of ciprofloxacin. The method showed sufficient accuracy with a mobile phase of only 10% organic composition showing advantage and trying to approach green chromatographic conditions.

ABSTRACT: A simple, sensitive and validated kinetic spectrophotometric method for the determination of certain mucolytic drugs namely acetylcysteine (Ac) and carbocisteine (Cc) is described. This method is based on the kinetic investigation of the reaction between the ...

A non-aqueous titration method has been reported in USPXXII for the assay of the raw material in addition to a HPLC method for determination of the drug in tablets . HPLC have been applied for the analysis of microquantities (nano-levels) of the drug in biological samples. Some of these methods involve several manipulation steps, which are not simple for routine analysis of pharmaceutical formulations and need sophisticated instruments. On the other hand, a few spectrophotometric [9-11] and polarographic [12,13] methods have been reported for famotidine determination as a drug substance or in commercial dosage forms. This paper describes the formation of a 1:1 ion-pair complex between famotidine and each of bromocresol green (BCG) and bromothymol blue (BTB) in order to develop a new spectrophotometric method for the drug determination. These results showed that the suggested method may be suitable for the routine quality control of famotidine in pharmaceutical formulations.

The compensation method and other chemometric methods (derivative, orthogonal function and difference spectrophotometry) have been applied to the direct determination of omeprazole, lansoprazole and pantoprazole in their pharmaceutical preparations. The methods have been validated; the limits of detection were found to be 3.3×10−2, 3.0×10−2 and 3.5×10−2 μg ml−1 for the three drugs, respectively. The repeatabililty of the methods were found to be 0.3–0.5%. The linearity ranges were found to be 0.5–3.5 μg ml−1. The proposed methods have been applied to the determination of the three drugs in their grastro-resistant formulations. The difference spectrophotometric (ΔA) method is unaffected by the presence of acid induced degradation products; hence can be used as a stability indicating assay.

Cyclic voltammetry (CV) is a unique technique for the electrochemical characterization of compounds by providing their oxidation/reduction potentials. This technique is widely used in evaluating antioxidants in the oil, food, diagnostic and agricultural industries; however, CV is rarely used in the development of pharmaceutical formulations. This review briefly describes the basic principles of CV and its application in other industries along with the potential and limitations of CV in the rapid evaluation of antioxidants in pharmaceutical formulations. An extensive survey of the literature shows that there is a good correlation between the oxidation potentials of various antioxidants and their antioxidant efficiency. In conclusion, CV should be useful in the development of pharmaceutical formulations where a small group of the preferred antioxidants is rapidly identified. This small group of the most preferred antioxidants can then be employed in a conventional drug stability study thereby providing a rapid approach for the selection of the most suitable antioxidant for a pharmaceutical formulation.

The electrochemical oxidation of salicylic acid (SA) has been studied on a glassy carbon electrode using cyclic voltammetry and differential pulse voltammetric (DPV) method. SA gives a single irreversible oxidation wave over the wide pH range studied. The irreversibility of the electrode process was verified by different criteria. The mechanism of oxidation is discussed. Using differential pulse voltammetry, SA yielded a well-defined voltammetric response in Britton-Robinson buffer solution, pH 2.37 at 1.088 V (versus Ag/AgCl). The method was linear over the SA concentration range: 1-60 g ml −1 . The method was successfully applied for the analysis of SA as a hydrolysis product, in solid pharmaceutical formulations containing acetylsalicylic acid (ASA).

The compensation method and other chemometric methods (derivative, orthogonal function and difference spectrophotometry) have been applied to the direct determination of omeprazole, lansoprazole and pantoprazole in their pharmaceutical preparations. The methods have been validated; the limits of detection were found to be 3.3×10−2, 3.0×10−2 and 3.5×10−2 μg ml−1 for the three drugs, respectively. The repeatabililty of the methods were found to be 0.3–0.5%. The linearity ranges were found to be 0.5–3.5 μg ml−1. The proposed methods have been applied to the determination of the three drugs in their grastro-resistant formulations. The difference spectrophotometric (ΔA) method is unaffected by the presence of acid induced degradation products; hence can be used as a stability indicating assay.

In present study, three new spectrophotometric methods, original UV spectrophotometry, first and second order derivative UV spectrophotometry, were developed for the determination of amoxicillin in pharmaceutical preparations. In original UV spectrophotometry, absorbances were measured at 247.0 nm in the zero order UV spectra of the solution of amoxicillin in 0. 1N NaOH in the range of 220 -350 nm. In first derivative UV spectrophotometry, dA/dX values were measured at 255.8 nm in the first derivative UV spectra of the solution of amoxicillin in 0. IN NaOH in the range of 220 -320 nm (Ak= 2 nm). In second derivative UV spectrophotometry a^A/dl 2 values were measured at 249.2 nm in the second derivative UV spectra of the solution of amoxicillin in 0. IN NaOH in the range of 220 -320 nm (AX= 4 nm). Linearity range was found as 3.2 -48.0 /ug/mL in all three methods. Mean recoveries and the relative standard deviations of the methods were found as 99.67 % and 1.20 % in original UV spectrophotometry at 247.0 nm, 99.04 % and 1.76 % in first derivative UV spectrophotometry at 255.8 nm and, 99.43% and 2.34 % in second derivative UV spectrophotometry at 249.2 nm respectively. Three spectrophotometric methods developed were successfully applied to 8 tablets, 2 oral suspensions and 1 lyophilized powder formulation commercially available in Turkish drug market. All the results were compared statistically with those obtained by using the methods indicated in USP XXIII Amoksisilin'in farmasotik preparatlarda spektrofotometrik miktar tayini Bu qalismada, amoksisilin'in farmasotik preparatlarda miktar tayini iqin uq yeni spektrofotometrik yontem, orijinal UV spektrofotometri, birinci ve ikinci turev spektrofotometri, gelistirilmistir. Orijinal UV spektrofotometride absorbans degerleri, amoksisilin in 0. IN NaOH iqerisindeki qozeltilerinin 220-350 nm araligindaki UV spektrumlannda 247.0 nm de dlqulmustiir. Birinci turevUV spektrofotometride, dA/dX degerleri, amoksisilin in 0. IN NaOH iqerisindeki qozeltilerinin 220-320 nm araligindaki birinci turev UV spektrumlannda (AX= 2 nm) 255.8 nm de dlqulmustiir. Ikinci turev UV spektrofotometride ^A/dX 2 degerleri amoksisilin in 0. IN NaOH iqerisindeki qozeltilerinin 220-320 nm araligindaki ikinci turev UV spektrumlannda (AX= 4 nm) 255.8 nm de dlqulmustiir. (Qalismada dogrusal qalisma araligi her uq yontem iqin de 3.2 -48.0 /ug/mL olarak bulunmustur. Yontemlerdeki ortalama geri kazanim ve bagil standart sapma degerleri sirasiyla orijinal UV spektrofotometride 247.0 nm de % 99.67 ve % 1.20, birinci turev UV spektrofotometride,255.8 nm de % 99.04 ve % 1.74 ve, ikinci turev UV spektrofotometride249.2 nm de % 99.43 ve % 2.35 olarak bulunmustur. Gelistirilen uq yontem Turkiye ilaq piyasasinda bulunan 8 adet tablet, 2 adet oral suspansiyon ve bir adet liyofilize toz formulasyonuna basariyla uygulanmistir. Elde edilen turn sonuqlar USP XXII de belirtilen yontemlerle elde edilenlerle istatistiksel olarak karsilastinlmistir.

In the last decades, the number of patients receiving chemotherapy has considerably increased. Given the toxicity of cytotoxic agents to humans (not only for patients but also for healthcare professionals), the development of reliable analytical methods to analyse these compounds became necessary. From the discovery of new substances to patient administration, all pharmaceutical fields are concerned with the analysis of cytotoxic drugs. In this review, the use of methods to analyse cytotoxic agents in various matrices, such as pharmaceutical formulations and biological and environmental samples, is discussed. Thus, an overview of reported analytical methods for the determination of the most commonly used anticancer drugs is given.

Different pharmaceutical preparations against the common cold containing phenylephrine (PHE) and saccharose were studied. New impurities were discovered in these preparations after exposure using isocratic ion-pair chromatography separation on a C18 column. LC-MS and NMR techniques were employed to identify and to fully characterize these new compounds. The products were identified as 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,8-diol and 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,6-diol. Identification of these degradation products allowed to understand and to confirm their formation mechanism. The developed HPLC method separates of all known impurities and impurities originated from PHE as well.

Titrimetric and spectrophotometric assay of pantoprazole sodium sesquihydrate (PSS) using cerium(IV) sulphate as the oxidimetric reagent is described. The methods are based on the oxidation of PSS with a measured excess of Ce(IV) sulphate followed by the determination of unreacted oxidant using different reaction schemes. In titrimetry, the unreacted oxidant was determined by back titration with ferrous ammonium sulphate (FAS) in sulphuric acid medium. Spectrophotometry involves the reduction of unreacted Ce(IV) sulphate with a fixed quantity of Fe(II). The resulting Fe(III) is complexed with thiocyanate and the absorbance is measured at 470 nm. In both the methods, the amount of Ce(lV) sulphate reacted corresponds to PSS concentration. Titrimetry is applicable over 1–10 mg range whereas in spectrophotometry, the calibration graph is linear in the range of 0.5–7.0 μg/mL and the calculated molar absorptivity value is 1.58 × 105 L/mol cm. The validity of the proposed methods was tested by analyzing pure and dosage forms containing PSS. Statistical treatment of the results reflects that the proposed procedures are precise, accurate and easily applicable to the determination of PSS in pure form and in pharmaceutical formulations.

Different pharmaceutical preparations against the common cold containing phenylephrine (PHE) and saccharose were studied. New impurities were discovered in these preparations after exposure using isocratic ion-pair chromatography separation on a C18 column. LC-MS and NMR techniques were employed to identify and to fully characterize these new compounds. The products were identified as 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,8-diol and 1-[5-(hydroxymethyl)-2-furyl]-2-methyl-1,2,3,4-tetrahydroisochinolin-4,6-diol. Identification of these degradation products allowed to understand and to confirm their formation mechanism. The developed HPLC method separates of all known impurities and impurities originated from PHE as well.

The Jerusalem Balsam, a remedy based on an ethanolic extract of a herbal mixture, was formulated in 1719 in the pharmacy of the Saint Savior monastery in the old city of Jerusalem. Having gained fame, the Jerusalem Balsam was replicated and prepared in Europe. One can still find variations of the formula in current pharmacopoeias (B.P., 1998. The Stationary Office, London, p. 1510; Sweetman, S.C., Blake, P.S., McGlashan, J.M., Parsons, A.V., 2002. Martindale: The Extra Pharmacopeia, 33rd ed. Pharmaceutical Press, London, p. 1101). We report here, five different formulas, all referred to as "The Jerusalem Balsam". Three of those formulas were translated and two of these translations are presented in the text. A third one is available as Supplementary data online. As the formulas originate from different historical periods, the Jerusalem Balsam may be a good case study of the development of pharmaceutical formulations over a 250 years period. One of the formulas, found in a manuscript form in the archive of the monastery, contains four plants: olibanum (Boswellia spp.), myrrh (Commiphora spp.), aloe (Aloe sp.) and mastic (Pistacia lentiscus L.). We conducted pharmacological assays on this four-plant formula. It showed anti-inflammatory, as well as anti-oxidative, and anti-septic properties.

Simple, rapid and sensitive spectrophotometric procedures are developed for the analysis of gabapentin in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of gabapentin as n-electron donor with ninhydrin and pi-acceptors namely, 2,3,5,6-tetrachloro-1,4-benzoquinone, chloranilic acid, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyanoethylene and 7,7,8,8-tetracyanoquinodimethane. The obtained complexes were measured at 568, 230, 314, 304, 335 and 439 nm for ninhydrin, chloranil, Chloranilic acid, DDQ, TCNE and TCNQ respectively. The proposed procedures could be successfully applied to the determination of gabepentin with good recovery; percent ranged from 99.3 to 100.7 The association constants and free energy changes using Benesi–Hildebrand plots are also studied.

In this article, the quantitative determination of acetylsalicylic acid (ASA) contained in two of the most commercially available pharmaceutical formulations was performed using differential scanning calorimetry (DSC) after a thermoanalytical characterization and a preliminary test on compatibility of ASA with three of the most commonly considered excipients [cellulose (CE), starch (ST) and sodium saccharin (SS)]. Finally, the analytical results obtained were compared with those derived by titrimetry and two UV spectrophotometric methods: i.e. a 'direct method' and a method based on first-order derivative UV spectra.

Natural penicillin (benzylpenicillin) is the oldest antibiotic observed by Alexander Fleming in 1928. To broaden its spectrum of activity, natural penicillin was modified, giving rise to a group of antibiotics under the name ‘penicillins’. Although an increasing number of bacteria appear to be resistant to them, penicillins are used to treat a variety of bacterial infections including Gram-positive, Gram-negative aerobic and anaerobic bacteria. Consequently, they are widely used in human and veterinary medicine to prevent and treat diseases. This review covers the analytical methodologies, mainly chromatographic, employed to the penicillins determination in pharmaceutical formulations, biological fluids and in production-scale fermentations reported in the literature. Results of published assays are comparatively presented focusing on sample preparation regarding isolation and purification, chromatographic conditions and method validation. Information on chemical structure, spectrum of activity and action mechanism of common penicillins has also been given.

A simple, rapid, sensitive and accurate spectrophotometric method for the determination of captopril in pure form and pharmaceutical formulations is developed. The procedure is based on the reaction of copper(II) with captopril in the presence of neocuproine (NC) (2,9-dimethyl-1,10phenanthroline) reagent in acetate buffer at pH 5.0. Copper(II) is reduced easily by captopril to Cu(I)-neocuproine complex, which shows an absorption maximum at 448 nm. Beer's law was obeyed in the concentration range 0.3-3.0 lg mL À1 with a minimum detection limit (LOD) of 0.039 lg mL À1 and a quantification limit (LOQ) of 0.129 lg mL À1 . For more accurate results, Ringbom optimum concentration ranges was 0.5-2.7 lg mL À1 . The apparent molar absorbtivity and Sandell sensitivity were calculated. The validity of the proposed method was tested by analyzing the pure and pharmaceutical formulations and compared well with those obtained by the official method and demonstrated good accuracy and precision.

Two improved, simple, selective and sensitive reversed-phase HPLC methods were developed for the determination of diosmin and hesperidin simultaneously or separately, using external or internal standard techniques, respectively. The methods were applied for determination of the diosmin and/or hesperidin in Buchu leaves and pharmaceutical dosage forms (three tablets). The methods involved very simple efficient extraction procedures, the use of a LiChrosorb RP-18 column, a mixture of methanol-water (60:40, v/v) as a mobile phase in an isocratic mode at a flow rate of 1.5 ml/min and UV detection at 345 nm. In all HPLC analysis the relative standard deviation did not exceed 1.9%. As low as 50 and 25 ng (per injection) could be detected in less than 6 min with a high degree of accuracy. This is the first report for the determination of the two flavonoids simultaneously in Buchu leaf and tablets containing them.

The laboratory toxicologist is frequently faced with the challenge of selecting appropriate vehicles or developing utilitarian formulations for use in in vivo nonclinical safety assessment studies. Although there are many vehicles available that may meet physical and chemical requirements for chemical or pharmaceutical formulation, there are wide differences in species and route of administration specific to tolerances to these vehicles. In current practice, these differences are largely approached on a basis of individual experience as there is only scattered literature on individual vehicles and no comprehensive treatment or information source. This approach leads to excessive animal use and unplanned delays in testing and development. To address this need, a consulting firm and three contract research organizations conducted a rigorous data mining operation of control (vehicle) data from studies dating from 1991 to present. The results identified 65 single component vehicles used in 368 studies across multiple species (dog, primate, rat, mouse, rabbit, guinea pig, minipig, chick embryo, and cat) by multiple routes. Reported here are the results of this effort, including maximum tolerated use levels by species, route, and duration of study, with accompanying dose limiting toxicity. Also included are basic chemical information and a review of available literature on each vehicle, as well as guidance on volume limits and pH by route and some basic guidance on nonclinical formulation development.