A stability study of ticlopidine products from 18 countries.

The results of the stability study of ticlopidine formulations (250 mg and 100 mg) show that products available in many countries worldwide exhibit different stability characteristics. Stability testing under the International Conference on Harmonization (ICH) accelerated test conditions (40 degrees C/75% relative humidity [RH], 3 and 6 months) was performed on a total of 43 products obtained from 18 countries. The samples were visually examined for physical change and analyzed for their content of degradation products, remaining ticlopidine, and in vitro dissolution characteristics (in the case of tablets). Only 6 (16%) of all the samples submitted to this study had a good stability profile. Their appearance remained unchanged during the study; assay results were between 95% and 100%; their impurity content did not exceed 0.25%; and in the dissolution test, at least 75% of ticlopidine was dissolved after 30 min. Three samples had excellent dissolution properties and showed a very high purity level (viz. 21, 40, and 43) over the course of the study.

Analysis of cefadroxil by micellar electrokinetic capillary chromatography: development and validation.

A method is developed and validated for analysis of the antibiotic cefadroxil using micellar electrokinetic capillary chromatography. It permits cefadroxil to be completely separated from ten of its known related substances within 15 min (including the washing procedure). The separation is performed in an acetate buffer (50 mM, pH 5.25) containing sodium dodecyl sulfate (SDS; 110 mM). The fused-silica capillary was 44 cm long (36 cm effective length), 50 microm ID; the voltage, 18 kV; temperature, 15 degrees C; and the detection wavelength; 254 nm. The influence of the type of buffer, buffer pH and concentration, and of the SDS concentration was investigated. The robustness of the method was examined by means of a full-fraction factorial design. The parameters for validation such as linearity, precision, limit of detection and limit of quantitation are also reported.

HPLC determination of sodium cromoglycate in pharmaceutical dosage forms.

A reversed-phase high-performance liquid chromatography (HPLC) method is described for the determination of sodium chromoglycate (SCG) in bulk drug and pharmaceutical dosage forms (capsules, solutions, gels). Aliquots were chromatographed on C18 columns using methanol: phosphate buffer (50:50 v/v) at pH 2.3 as the mobile phase. Detection was performed at 326 nm with a linear range of 0.05-0.5 microgram/ml (r = 0.9999). Recovery values ranged from 99.21 to 106.31% (N = 9). The proposed method is rapid and simple, free from interference by excipient and degradation products, and can be recommended for routine control analysis of sodium chromoglycate commercial products and magistral formulations.

Determination of sodium cromoglycate in pharmaceutical dosage forms using TLC-densitometry.

A TLC-UV densitometric method for the determination of sodium cromoglycate (SCG) in ophthalmic solutions, gels and capsules has been developed. After TLC separation of active substance on silica gel GF254 using methanol-water-ethylacetate (15:45:40 v/v/v) as the mobile phase, densitometric measurements were performed with HPTLC scanner at 254 nm. The proposed method is rapid and simple, free from interference by adjuvants and can be suggested for the routine analysis of sodium cromoglycate.

Investigation of the pindolol-Fe(III) complex and its use in the spectrophotometric determination of pindolol in bulk drug and tablets.

It was found that pindolol reacts with Fe(III) chloride producing a green water soluble complex (1:1, v/v) with maximum absorbance at 635 nm. By applying the methods of Sommer and Job [Sommer et al., Folia, tomus XI, Chemia 7, 25, 1970] the conditional stability constant of the complex at pH = 1.70 +/- 0.02 was found to be log K' = 4.95 and the molar absorptivity of the complex to be 206 l mol-1 cm-1. Beer's law was obeyed up to a concentration of 220 mumol l-1 of pindolol. The recoveries were 98-101% (n = 7) and the detection limit was 5 micrograms ml-1. The described method was sufficiently simple, selective and sensitive to be suitable for the rapid and accurate determination of pindolol in tablets.

Statistical optimization applied to the spectrophotometric study of a tolmetin-copper(II) complex.

Tolmetin sodium has been investigated and determined from dosage forms as its Cu(II) complex and method optimized by statistical optimization. The assay was developed using two mathematical statistical models: factorial design and response-surface mapping. The decision to apply experimental design techniques to the development of the method was made after a series of screening experiments revealed that the complex formation and extraction are maximized as a function of supporting electrolyte concentration, concentration of Cu(II) acetate and pH of the reaction mixture. One set of two-level three variable factorial experiments was carried out in order to evaluate the main effect, as well as the interaction among factors. The final step was to optimize the values of variables using response surface design. The best set of conditions was selected for further investigation.

Spectrophotometric determination of oxprenolol hydrochloride as its Fe (III) complex.

A spectrophotometric determination of oxprenolol hydrochloride in pharmaceutical preparations is described. The method is based on the reaction of oxprenolol hydrochloride with Fe (III) ion in the presence of ammonium thiocyanate, in acid media. The complex formed between oxprenolol hydrochloride and Fe (III) ion was extracted with chloroform and assayed spectrophometrically at 477 nm. The results obtained are reproducible and hence the method is suitable for the determination of oxprenolol hydrochloride in pharmaceutical dosage forms.

Investigation of penbutolol-iron (III) complex and its spectrophotometric determination in tablets.

It has been established that penbutolol reacts with iron(III) chloride in the presence of ammonium thiocyanate to form a pink complex (2:1) that is soluble in chloroform with a maximum absorbance at 478 nm. By application of the methods of Sommer and Job involving non-equimolar solutions, the conditional stability constant (log k') of the complex at the optimum pH of 1.5 +/- 0.02 and an ionic strength of (mu) 0.14 M, was found to be 5.769. The molar absorptivity at 478 nm was 136 1 mol-1 cm-1 at pH 1.5 +/- 0.02. The validity of Beer's law has been tested in the concentration range 3-18 x 10(-4) M; the relative standard deviation (n = 8) was 1.52-3.21%. The proposed method was found to be suitable for the accurate, simple and rapid analysis of penbutolol in the bulk drug and in tablets.