Stability-indicating green HPLC method for fixed-dose tablets containing remogliflozin etabonate and teneligliptin: an AQbD approach.

BACKGROUND: In June 2021, the Central Drug Standards Control Organization approved a fixed-dose combination tablet containing remogliflozin etabonate (100 mg) and teneligliptin (10 mg) to manage type II diabetes. OBJECTIVE: This study aims to develop a stability-indicating RP-HPLC method for quantifying remogliflozin etabonate and teneligliptin in tablet formulations via analytical quality by design (AQbD) principles. METHODS: Risk assessment, Plackett-Burman design, and central composite design were employed to understand the impact of independent variables on critical analytical attributes. The stationary phase was a HyperClone BDS C18 column, and the mobile phase consisted of acetonitrile and phosphate buffer (20 mM, pH 5) at a 45:55% (v/v) ratio. RESULTS: The method, validated per ICH Q2 (R1), resulted in retention times of 3.395 and 12.308 min for teneligliptin and remogliflozin etabonate, respectively. Forced degradation studies confirmed robustness, with clear peak separation and no interference from degradation products. The AGREE score of 0.65 supports its green applicability for tablet analysis in quality control. CONCLUSION: The AQbD-assisted RP-HPLC method developed in this study offers environmental friendliness, efficient separation with well-defined peaks, and simple mobile phase combination.

Stability-indicating HPLC for remogliflozin, vildagliptin, and metformin: Method development, validation, and greenness.

OBJECTIVE: The present work represents a reverse-phase high-performance liquid chromatography method in addition to stability studies for sequential estimation of remogliflozin etabonate, vildagliptin, and metformin HCl in tablet formulation. METHOD: The mentioned method utilizes a Phenomenex Luna C18 column (250×4.6mm, 5µm). It consists of a column oven's temperature of 35°C. Mobile phase includes a mixture of 50% phosphate buffer (pH - 6.8) and 50% acetonitrile along with a flow rate of 0.8mL/min and 20minutes of run time. The injection volume was 20µL; 217nm is a detection wavelength, and a PDA detector is used for detection. RESULTS: The suggested technique was proven and validated per the ICH Q2 (R1) guideline. The combination was put under stress conditions that included acid, base, thermal, photolytic, and oxidative degradation. The combination was considerably degraded under oxidative, acidic, and basic circumstances for deterioration, and the degradation results were accurately identified from the observed peaks, demonstrating the method's effectiveness in detecting stability. CONCLUSION: The technique was quick, precise, sensitive, and accurate; as a result, it may be used in quality control laboratories and the pharmaceutical industry for routine quality monitoring of tablets containing all three medications.

Development and Validation of a New Reversed Phase HPLC Method for the Quantitation of Azithromycin and Rifampicin in a Capsule Formulation.

This research aimed to develop a new method for simultaneously estimating the presence of azithromycin (AZT) and rifampicin (RIF) in a capsule formulation using reverse-phase high-performance liquid chromatography. The developed method utilized a Gemini column with a 60:40% v/v acetonitrile and potassium dihydrogen phosphate mobile phase, a flow rate of 1 mL/min, and an injection volume of 20 µL. The detection wavelengths of 210 and 254 nm for AZT and RIF, respectively, were used. Validation ensures specificity with a peak purity index > 0.99999 for AZT and >0.99995 for RIF, affirming unambiguous analyte detection. The system suitability test, within acceptable limits, validates method reliability. Linearity calibration curves (R2 = 0.998) cover a 25-150% target concentration range. Accuracy studies employing the standard addition method yield recovery values between 96.6 and 103.9% for both drugs, confirming method accuracy. Precision studies reveal % relative standard deviation values consistently below 2%, highlighting reproducibility. Robustness testing supports method reliability under varying conditions. Application to a pharmaceutical capsule formulation demonstrates the method's practicality, accurately quantifying AZT (98.30%) and RIF (99.37%). This study provides a validated analytical approach for simultaneous quantification in commercial pharmaceutical products containing both drugs, enhancing pharmaceutical quality control for critical antibiotics in complex formulations.

Separation and quantification of azelnidipine and chlorthalidone in a synthetic mixture using optimized HPTLC method.

OBJECTIVES: A simple, accurate, and reliable high-performance thin-layer chromatographic technique has been developed and validated for the simultaneous quantitation of azelnidipine and chlorthalidone in bulk and synthetic mixtures. MATERIAL AND METHODS: The procedure was carried out using a precoated silica gel 60 F254 TLC plate with a mobile phase of chloroform, ethyl acetate, and methanol in the ratio of 6.5:3.5:0.6 (by volume). Thin-layer chromatographic densitometry at 240nm was used to quantify medicines chromatographically. RESULTS: Over concentration ranges of 250.0 to 1000.0ng/band for chlorthalidone and 160.0 to 640.0ng/band for azelnidipine, the high-performance thin-layer chromatography technique was quantitated. This technique produced a tight and well-resolved band at retention factors of 0.67±0.02 and 0.24±0.02 for azelnidipine and chlorthalidone, respectively. Data from a linear regression study calibrating this method revealed a strong linear correlation between the two approaches, with regression coefficients of r2>0.99 for both. According to The International Conference for Harmonization of Technical Requirements for Pharmaceuticals for Human Use requirements, the procedures were validated for precision, robustness, accuracy, and specificity. CONCLUSION: The developed method was also used to simultaneously estimate azelnidipine and chlorthalidone in a synthetic mixture. The results were found to be in exemplary % assay with label claims.

Analytical Quality by Design-Based Robust RP-HPLC Method for Quantitative Estimation of Pregabalin and Etoricoxib in Fixed-Dose Combination Tablet Formulation.

BACKGROUND: The Central Drugs Standard Control Organization approved a bilayered, uncoated, fixed-dosage combination tablet formulation containing pregabalin (75 mg) and etoricoxib (60 mg) in November 2019 to control prolonged back pain with neuropathic components. OBJECTIVE: This research aims to create an analytical quality by design-assisted reversed phase (RP)-HPLC method for quantifying pregabalin and etoricoxib in tablet formulation. METHODS: The best chromatographic conditions were a Phenomenex C8 column (250 × 4.6 mm, 5.6 µm) and a mobile phase of 0.35% orthophosphoric acid -acetonitrile (1 + 1, by volume). A flow rate of 1 mL/min was used with a detection wavelength of 220 nm. RESULTS: The optimized reversed phase HPLC method was successfully validated by the International Conference on Hormonization guideline Q2(R1). Moreover, the percentage assay of pregabalin and etoricoxib tablet formulation was 99.05 and 100.02% w/w, respectively, using the validated RP-HPLC method. CONCLUSION: The newly developed analytical quality by design-assisted RP-HPLC method has several advantages, including shortened analytical time (2.65 min and 7.45 min pregabalin and etoricoxib, respectively), efficient separation in terms of well-defined peaks, and a simple mobile phase combination. HIGHLIGHTS: The use of analytical quality by design principles and the design of the experiment tool allowed the detection of influential parameters critical for achieving the most favourable chromatographic conditions for accurately quantifying individual drugs using the RP-HPLC method. The compliance of the results with the ICH criteria validated the method. As a result, adopting the analytical quality by design methodology ensured the development of a more robust method that can generate consistent, dependable, and quality data throughout the process while also saving time.

A Critical Review on Analytical Methods for Recently Approved FDC Drugs: Pregabalin and Etoricoxib.

Fixed-dose combinations (FDCs) refer to products containing two or more active ingredients combined in a single dosage form. The FDCs are justified because of several advantages. These are a) potentiating therapeutic efficacy, b) reducing the incidences of adverse drug effects, c) having pharmacokinetic advantages, d) reducing pills burden, e) reducing the dose of individual drugs and f) decreasing the drug resistance development. A recently approved FDC of Pregabalin IP (75 mg) and Etoricoxib (60 mg) recommended to control neuropathic chronic back pain. Analytical methods are available for individual quantitation of pregabalin (PGB) and etoricoxib (ETC), but an effective and reliable analytical method has not been reported for their combination. Thus, the objective of this literature survey was to gather information on various analytical instrumental methods used so far for the individual quantitation of PGB and ETC in various matrices. Such data would be useful to the scientific community to develop a novel analytical method for the analysis of recently approved FDC of PGB and ETC. Various scientific databases were explored to meet the objectives, and the information is synchronized. The reported methods are high-performance liquid chromatography (48% & 53%), hyphenated techniques (54% & 21%), spectroscopy (50% & 34%), and high-performance thin-layer chromatography, or thin-layer chromatography (6% & 13%) for pregabalin and etoricoxib, respectively. All these methods were specific and selective for the analysis of individual drugs.

Development of Bioadhesive Buccal Tablets of Nicorandil Using a Factorial Approach.

OBJECTIVES: In the present investigation, bioadhesive buccal tablets were prepared using the sustained-release polymer hydroxypropyl methylcellulose (HPMC) K100M, bioadhesive polymer neem gum, and an impervious backing layer of ethyl cellulose. Nicorandil is sensitive to the first-pass effect; therefore, a buccal-adhesive dosage form can avoid this effect. MATERIALS AND METHODS: We used the direct compression technique to prepare the tablet formulation. A 32 full factorial design was composed in which the amounts of HPMC K100M (X1) and neem gum (X2) were chosen as the independent variables and the dependent variables were the percentage drug release at 6 h (Y1) and mucoadhesive strength in grams (Y2). Various in vitro parameters, i.e. thickness, friability, hardness, weight variation, surface pH, moisture absorption ratio, dissolution studies, and drug release kinetics, and ex vivo parameters like mucoadhesive strength and mucoadhesion time were determined for the prepared tablets. We subjected the optimized batch to a comparison with the marketed formulation and stability studies were performed. RESULTS: The formulation containing a 50:50 ratio of neem gum and HPMC K100M (F5) was considered optimum. The zero-order release kinetics model best fitted the optimized batch release profile, suggesting the system would release the drug at a constant rate. CONCLUSION: The release by the optimized formulation of the drug at a sustained rate along with its bioadhesive nature showed that the buccal route can be an option for the administration of nicorandil.