DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD FOR SIMULTANEOUS ESTIMATION OF CLIDINIUM BROMIDE, RABEPRAZOLE, CHLORDIAZEPOXIDE AND DICYCLOMINE HYDROCHLORIDE

Clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride(COLIWIN-R) drug combinations are used for the treatment of gastric acidity, anxiety, intestinal ulcers, abdominal cramps, irritable bowel syndrome and abdominal pain. A high performance liquid chromatographic method has been developed and validated for the simultaneous determination of clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride in capsules dosage forms using WATERS C18 column (50 mm × 4.6 mm, 5 µm) with mobile phase consisting of methanol, acetonitrile and phosphate buffer 40:30:30 (V/V) (0.05M, pH 4.0 adjusting with 0.5% ortho phosphoric acid) at a flow rate of 1.0 mL/ min monitoring the effluents at 220 nm. The retention times of clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride in capsule formulation were found to be 2.9 min, 3.5 min, 4.7 min, and 8.0 min, respectively. The method was validated according to the ICH guidelines for specificity, LOD, LOQ, precision, accuracy, linearity, ruggedness and robustness. The method show good reproducibility and recovery with % RSD less than 2. The proposed method was found to be simple, specific, precise, accurate and linear. Hence, it can be applied for routine analysis of clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride in pharmaceutical combined dosage forms.

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF CLIDINIUM BROMIDE, CHLORDIAZEPOXIDE AND DICYCLOMINE HYDROCHLORIDE IN TABLET DOSAGE FORM

A simple, specific, accurate reversed phase high performance liquid chromatographic method was developed for the simultaneous estimation of clidinium bromide, chlordiazepoxide and dicyclomine hydrochloride. Chromatographic separation of the three drugs was performed on a Chromatopak C-18 column (25 cm x 4.6 i.d. x 5µm) as the stationary phase with a mobile phase composed of 0.1 % triethylamine in water pH adjusted by 5 % o-phosphoric acid and acetonitrile in the ratio 30:70 at a flow rate of 0.8mL/min, Detection was carried out at 210 nm. The retention times of clidinium bromide, chlordiazepoxide and, dicyclomine hydrochloride were found to be 3.9 min, 5.4 min, and 6.8 min, respectively. The proposed method was validated for linearity, accuracy, precision, LOD and LOQ.

Evaluation of the Efficiency of Smart Stability-Indicating Spectrophotometric Methods Based on Mathematical and Statistical Processing of the Obtained Results Via Different Manipulating Pathways

Background: Smart different stability-indicating spectrophotometric methods have been established for the assay of chlordiazepoxide and clidinium bromide without the intervention of alkaline degradate of clidinium via various and different manipulating pathways without previous separation steps. Objective: The specificity of the established methods was inspected by analysing mixtures of cited drugs in the existence of the alkali-induced degradation product. Methods: These methods were employed either on scanned zero-order absorption spectra using absorbance subtraction, dual wavelength and Q-absorbance ratio or the amplitudes of the ratio spectra of zero-order absorption spectra like amplitude modulation and by derivative techniques to the ratio spectra as a derivative ratio method. In addition, the absorbance of the recovered zero-order absorption spectra was applied by successive ratio subtraction coupled with constant multiplication. Finally, the pathway depends on the amplitudes of the derivative spectra, successive derivative subtraction coupled with constant multiplication. The ranges of linearity were (1-12µg/mL) for chlordiazepoxide and (3- 12µg/mL) for clidinium bromide. Results: The outcomes achieved by the prospective methods were in consent with those of the official and reported methods when statistically compared using student’s t test, F-test and one-way ANOVA where no significant difference was detected with suitable precision, proving the absence of any important difference in accuracy and precision between them. They were confirmed in accordance with International Conference on Harmonization guidelines. Conclusion: The established methods can be considered as alternative methods for the routine determination of this fixed dose combination with minimum sample preparation.

Novel Stability-Indicating Chemometric-Assisted Spectrophotometric Methods for the Determination of Chlordiazepoxide and Clidinium Bromide in the Presence of Clidinium Bromide’s Alkali-Induced Degradation Product

Two simple and accurate chemometric-assisted spectrophotometric models were developed and validated for the simultaneous determination of chlordiazepoxide (CDZ) and clidinium bromide (CDB) in the presence of an alkali-induced degradation product of CDB in their pure and pharmaceutical formulation. Resolution was accomplished by using two multivariate calibration models, including principal component regression (PCR) and partial least-squares (PLS), applied to the UV spectra of the mixtures. Great improvement in the predictive abilities of these multivariate calibrations was observed. A calibration set was constructed and the best model used to predict the concentrations of the studied drugs. CDZ and CDB were analyzed with mean accuracies of 99.84 ± 1.41 and 99.81 ± 0.89% for CDZ and 99.56 ± 1.43 and 99.44 ± 1.41% for CDB using PLS and PCR models, respectively. The proposed models were validated and applied for the analysis of a commercial formulation and laboratory-prepared mixtures. The developed models were statistically compared with those of the official and reported methods with no significant differences observed. The models can be used for the routine analysis of both drugs in QC laboratories.