Content uniformity and dissolution tests of triplicate mixtures by a double divisor-ratio spectra derivative method.

The use of a UV double divisor-ratio spectra derivative calibration for the simultaneous analysis of synthetic samples and commercial tablet preparations without prior separation is proposed. The method was successfully applied to quantify three ternary mixtures, chlorpheniramine maleate and caffeine combined with paracetamol or acetylsalicylic acid and a mixture of acetylsalicylic acid combined with paracetamol and caffeine, using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0.84-4.21 microg/ml for chlorpheniramine maleate, 1.60-15.96 microg/ml for caffeine, 2.0-20.0 microg/ml for acetylsalicylic acid and 1.58-15.93 microg/ml for paracetamol. The whole procedure was applied to synthetic mixtures of pure drugs as well as to commercial preparations (Algon) by using content uniformity and dissolution tests (USP 24) and was found to be precise and reproducible. According to the dissolution profile test more than 84% of paracetamol and caffeine were dissolved within 20 min. Acetylsalicylic acid dissolved more slowly, taking about 45-60 min to dissolve completely. A chemometric method partial least squares (PLS) and a HPLC method were also employed to evaluate the same mixtures. The results of the proposed method were in excellent agreement with those obtained from PLS and HPLC methods and can be satisfactorily used for routine analysis of multicomponent dosage forms.

Application of two chemometric methods for the determination of imipramine, amitriptyline and perphenazine in content uniformity and drug dissolution studies.

Double-divisor spectra derivative and partial least squares methods were developed for content uniformity and dissolution tests in binary or ternary mixtures. The simultaneous determinations of perphenazine (PER) combined with amitriptyline hydrochloride (AMI) and/or imipramine hydrochloride (IMI) have been accomplished using the information of the absorption spectra of appropriate solutions. The double-divisor method is based on the use of the first derivative of the ratio spectrum obtained by dividing the absorption spectrum of the ternary mixture PER-AMI-IMI by a standard spectrum resulted from the addition of two of the three analytes in equal concentrations. The concentration of each component is then determined from their respective calibration graphs established by measuring the ratio derivative analytical signal at a specific wavelength. In this method, the linear determination ranges were of 3.65-18.24 microg/mL for PER, 4.32-21.60 microg/mL for AMI, and 4.83-24.19 microg/mL for IMI. The results were compared with those obtained by partial least squares multivariate calibration (PLS) method pre-treated by a wavelet compression-orthogonal signal correction (W-OSC) filter in zero-order derivative spectra. The calibration model was evaluated by internal validation (cross-validation) and by external validation over synthetic mixtures, content uniformity and dissolution tests. According to the dissolution profile test more than 95% of the three substances were dissolved within 10 min. The results from both techniques were statistically compared with each other and can be satisfactorily used for quantitative analysis and dissolution tests of multicomponent tablets.

Chemometric and derivative methods as flexible spectrophotometric approaches for dissolution and assaying tests in multicomponent tablets.

Two derivative spectrophotometric (ratio derivative spectra and algorithm bivariate calibration) and a chemometric methods (partial least squares, PLS) are proposed for the simultaneous determination of binary mixtures in tablet analysis and dissolutions tests, without prior separation. These approaches are successfully applied to quantify trimethoprim (TMP) combined with sulfamethoxazole (SMX) or sulfamethazine (SMZ) or sulfafurazole (SFZ) using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0.98-17.5 microg/ml for TMP, 0.95-17.2 microg/ml for SMX, 1.16-17.5 microg/ml for SMZ and 0.97-17.4 microg/ml for SFZ. The first derivative (1D) bivariate algorithm method involves the use of four calibration curves: two for each compound at two different wavelengths, selected by Kaiser's method. Similarly, the first derivative ratio spectrophotometry employs the linear relationship between the ratio spectra of the analytes and the concentration range. The results were compared with those obtained by PLS multivariate calibration. The calibration models from PLS were pre-treated by orthogonal signal correction and evaluated by cross-validation using the 'SIMCA-P 9' software. Synthetic mixtures of TMP and sulfonamides were used in five different sets for the validity of the calibrations. Mean recoveries for derivative ratio, derivative bivariate and PLS methods were found to be between 99.7% and 102.0% for TMP, 99.4% and 100.2% for SMX, 99.3% and 101.0% for SMZ and 98.1% and 102.3% for SFZ. The calibrations of the three methods were successfully applied to the assaying and dissolution of placebo and commercial tablets without any prior separation. More than 85% of TMP, SMX and SMZ were dissolved within 15 min. For SFZ, only 85% of the compound was dissolved after 60 min. In this study, the three spectrophotometric methods can be satisfactorily used for the quantitative analysis and for dissolution tests of multicomponent dosage forms.

Determination of butamyrate citrate in cough preparations by derivative UV spectrophotometry and high performance liquid chromatography.

Derivative spectrophotometric procedures and an isocratic high performance liquid chromatographic method for the determination of butamyrate citrate (Sinecod, Safarol) in cough syrups have been developed. In the spectrophotometric method, direct measurement of the drug at its absorption maxima is impossible because of interference from different absorbing excipients. Extraction of butamyrate citrate was performed with n-pentane/isopropyl alcohol. Quantification was carried out through the use of 1D derivative at a trough depth of 253.6 nm where interferences from other coextracted compounds are negligible. The extraction efficiency expressed as a % recovery and precision were assessed by fortifying placebo syrup(s) with known amounts of the compound. Also, a reversed phase high performance liquid chromatographic method was used with a mobile phase containing 0.015 M aqueous tetraethylammonium hydrogen sulfate, methanol and acetonitrile 40:30:30 adjusted to pH 3.50 with ammonium hydroxide. The retention behavior of butamyrate citrate as a function of both pH and salt concentration in the aqueous portion of the mobile phase was investigated. Quantification was achieved with UV detection at 258 nm based on peak area. The HPLC method clearly separates the analyte from its degradation products derived after storage of samples under different stress conditions such as acid, alkaline, temperature, oxygen and light. The described methods were successfully applied to the determination of butamyrate citrate in commercial pharmaceutical products and in placebo syrups prepared in the laboratory with good accuracy and precision. The results of the present study show that the use of the derivatives and the HPLC procedure provide precise and sensitive methods for the determination of the compound in pharmaceutical formulations.