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.

Stability Indicating RP-UPLC Method for Simultaneous Estimation of Rabeprazole Sodium and Mosapride Citrate in Tablet Dosage form

RP- UPLC method was developed and validated for the simultaneous determination of Rabeprazole sodium and Mosapride citrate in tablet dosage form. The separation was achieved on a BEH C18 (50mm × 2.1mm× 1.7µm) column using mobile phase of Ammonium acetate buffer: Acetonitrile (60:40% v/v). The flow rate was 0.4 ml/min and detection was carried out at 270nm and column oven 35ºC. Rabeprazole sodium and Mosapride citrate was subjected to stress condition including Acidic, Alkaline, Oxidation, Photolysis and Thermal degradation. This method was validated as per ICH (Q2R1) guideline.

COMEDICATION OF RABEPRAZOLE SODIUM CAUSES POTENTIAL DRUG-DRUG INTERACTION WITH DIABETIC DRUG LINAGLIPTIN: In-vitro AND In-silico APPROACHES

Drug-drug interaction is a notable concern among physicians when prescribing multi-therapy to the patients as concomitant administration of multi-drugs might cause unexpected adverse drug reactions. The main objective of this research is to predict a potential drug-drug interaction between two frequently used drugs by diabetic patients, an antidiabetic drug (linagliptin) and a proton pump inhibitor (rabeprazole sodium). Here, several in vitro techniques, including thermal (melting point, thermogravimetric analysis [TGA]), morphological (scanning electron microscopy [SEM] and X-ray powder diffraction [XRPD] analysis), highly sophisticated synchronous fluorescence, and in silico methods were applied to anticipate the potential drug-drug interaction between these stated drugs quickly. The melting point and TGA study revealed thermochemical properties, thermal stability profiles, and degradation patterns upon temperature rising of the formed complex and these precursor drugs. The SEM and XRPD have provided the morphological changes like particle shape and size distribution of the desired molecule that might be caused due to the potential drug-drug interactions. Besides, the drastic reduction of the quenching rate constant of linagliptin during interaction with bovine serum albumin in synchronous fluorescence also endorsed the potential drug-drug interaction. Furthermore, the drug-receptor docking analysis demonstrated that the binding affinity of the precursor ligands might be reduced due to the predicted drug-drug interaction. However, the current evidence warrants extensive investigation to confirm the above-stated potential drug-drug interaction in the larger animal model. Finally, clinical data need to be closely monitored during the treatment of diabetic patients prescribed with linagliptin and rabeprazole sodium.

Green Atomic Absorption Spectroscopic Methods for the Determination of Rabeprazole Sodium and Fluvastatin Sodium in Pure and Pharmaceutical Dosage Forms

Aims: Novel green analytical methods have been proposed for the assay of Rabeprazole sodium and Fluvastatin sodium in their pure and formulated dosage forms. Study Design: The methods determine each drug through the estimation of its sodium content, using Flame Atomic Absorption Spectroscopy at wavelength 589 nm. Place and Duration of Study: Central laboratory at Faculty of Pharmacy, Damanhour University. Time duration January-March, 2020. Methodology: Methods are developed and optimized for maximum sensitivity, selectivity and degree of greenness. Linearity is achieved in the range of 8.29- 66.33 ppm of Rabeprazole sodium (equivalent to 0.5- 4 ppm Na) and 14.13- 141.32 ppm of Fluvastatin sodium (equivalent to 0.75 -7.5 ppm Na). The proposed assays are fully validated regarding ICH guidelines. Results: Atomic spectroscopic assays are compared to reported spectrophotometric ones for each drug separately using Student t-test and F-variance ratio. Conclusion: Satisfactory values indicate good agreement and the insignificant difference between both methods. The obtained percentages of recovery (99-101%) indicate no interference from excipients in formulation matrices.

Development of Validated Stability-indicating High Performance Thin Layer Chromatography Method for Estimation of Rabeprazole Sodium and Aceclofenac in Bulk Drug

Objective: To develop a validated stability-indicating high performance thin layer chromatography method for the estimation of Rabeprazole Sodium (RZL) and Aceclofenac (ACF) in bulk drugs. Methods: A high performance thin layer chromatographic (HPTLC) method has been developed for the separation of RZL & ACF on plates precoated with aluminium back silica gel 60 F254. Different mobile phases were used on trial and error basis for separation of two drugs. The final mobile phase selected for analysis was toluene: ethyl acetate: methanol: acetic acid: ammonia in the ration of 6:4:1:0.2:0.1 (v/v). Both the drugs showed maximum absorbance at 279 nm which was selected as the detection wavelength throughout the experimental work. Developed method was validated as per ICH guidelines. Forced degradation of drugs was carried out under various stress conditions and HPTLC method was used for analysing the stability of drugs. Results: HPTLC method was successfully developed for separation of RZL and ACF with clear separation of bands of the drugs. Method validation after assessment of various parameters indicated low % RSD within an acceptable limit of < 2.0 and the stability studies indicated the satisfactory separation of both the drugs from that of degraded products with considerable % recovery profile. Conclusion: The developed method is rapid, reliable, precise, and reproducible and demonstrates the suitability of the method for stability determination of rabeprazole and aceclofenac.

An application of continuous flow microreactor in the synthesis and extraction of rabeprazole

The oxidation of rabeprazole sulfide is a key step in the synthesis of rabeprazole, a drug for the treatment of stomach acid-related disorders. The current rabeprazole production process adopts one pot batch process, which has low reaction efficiency and poor stability. A continuous process can greatly improve the production efficiency and solve the above problems. Therefore, the reaction parameters of rabeprazole in microreactor were explored through laboratory experiments to explore the possibility of continuous production of rabeprazole. Rabeprazole sodium was synthesized by using rabeprazole thioether as a raw material and sodium hypochlorite solution as the oxidant. Oxidation, quenching, acid-base regulation and extraction were completed continuously in the microreactor. Rabeprazole solution with a purity of 98.78% (±0.13%) can be obtained continuously in 56 s, whereas intermittent production lasted for at least 2 h. Thus, the microreactor can effectively improve the oxidation synthesis efficiency of rabeprazole, and provide reference for the realization of other reactions in the microreactor.