Zero-crossing UV spectrophotometer with third derivative for the simultaneous determination of vildagliptin and metformin in a combination tablet

Abstract

A UV spectrophotometer with third derivative zero-crossing measurement, configured for the simultaneous determination of vildagliptin and metformin in combined tablet form, consisting of an ultraviolet optical measuring system, a digital signal processor and a software module for derivative calculation.

Description

AREA OF INVENTION

[0001] The invention relates to the field of pharmaceutical analysis and spectrophotometric measuring systems. In particular, it relates to a UV spectrophotometer with third-derivative zero-crossing measurement for the simultaneous quantification of vildagliptin and metformin in combination preparations in tablet form using distilled water as a solvent. The instrument ensures accuracy, precision, and compliance with the ICH (International Council for Harmonisation) guidelines for analytical validation. BACKGROUND OF THE INVENTION

[0002] Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia due to insulin resistance or deficiency. Combination therapy with vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin, a biguanide, is frequently prescribed for blood glucose control in patients with type 2 diabetes. Analytical quantification of these two active ingredients in a combination formulation is essential for routine quality control and formulation validation.

[0003] Conventional methods for determining such combinations include high-performance liquid chromatography (HPLC) and other complex chromatographic techniques. While precise, these require expensive solvents, lengthy processing times, and sophisticated instrumentation. There is a need for a simpler, faster, more environmentally friendly, and cost-effective system that can simultaneously determine both active ingredients with high precision and reproducibility using readily available laboratory resources.

[0004] UV spectrophotometry with zero-crossing measurement and third derivative enables the simultaneous analysis of multicomponent systems by eliminating spectral overlaps through mathematical differentiation. However, the lack of a standardized instrument and a suitable analytical configuration for the analysis of drug combinations has limited its application to date. The present invention overcomes these challenges with a specially configured spectrophotometric system featuring optimized wavelength detection and analytical precision, suitable for the simultaneous determination of vildagliptin and metformin. SUMMARY OF THE INVENTION

[0005] The invention relates to a third-derivative UV spectrophotometer with zero-crossing detection for the simultaneous determination of vildagliptin and metformin in a combination drug formulation. The system uses a spectrophotometer in derivative mode with optimized wavelength sensitivity for the detection of vildagliptin at 217 nm and metformin at 230 nm in distilled water as solvent. The device integrates data acquisition software for automatic derivative calculation and zero-crossing detection, thus providing accurate, linear, and reproducible results.

[0006] The analyzer features integrated calibration, precision validation, and recovery analysis functions to ensure compliance with ICH guidelines. Linearity according to the Lambert-Beer law is maintained for vildagliptin in the concentration range of 2–10 µg / ml and for metformin in the range of 10–50 µg / ml, with correlation coefficients of 0.9988 and 0.9992, respectively. The instrument guarantees reliable accuracy (recovery 99–100%) and precision (RSD < 2%) and is therefore suitable for routine quality control and laboratory validation of combination antidiabetic drugs. DETAILED DESCRIPTION

[0007] The invention describes a spectrophotometric analyzer with a UV / VIS spectrophotometer for the spectral analysis of third derivatives and for determining zero crossings. The device enables the simultaneous determination of two or more pharmaceutical active ingredients with overlapping absorption spectra.

[0008] The device includes: a) a UV-optical measuring unit capable of scanning the wavelength range from 200 to 400 nm with an accuracy of ±0.1 nm; b) a digital signal processing module for converting raw absorption data into third-derivative spectral curves; c) a zero-crossing detection algorithm integrated into the analysis software; and d) a calibration and data validation interface for verifying linearity, accuracy and precision.

[0009] The instrument's sample chamber accommodates standard quartz cuvettes containing tablet extract solutions with distilled water as the solvent. The third-derivative spectral mode eliminates background noise and spectral overlap between vildagliptin and metformin. At the zero crossings (217 nm for vildagliptin and 230 nm for metformin), each analyte can be quantified without mutual interference.

[0010] The instrument is calibrated using reference standards for both active ingredients within their respective linear ranges. The system automatically calculates calibration curves, correlation coefficients, and regression equations, thus ensuring reliable quantification. The integrated analysis module enables the determination of precision within a single day and between different days, recovery validation, and robustness testing according to ICH Q2 (R1).

[0011] The instrument is characterized by high repeatability and robustness with minimal solvent consumption. Results demonstrate precise linearity across the entire measuring range and a recovery rate between 99 and 100%, confirming the system's analytical accuracy. The design ensures ease of use, rapid analysis, low operating costs, and adherence to the principles of green chemistry through the use of water as a solvent.

[0012] The device can be used in the pharmaceutical industry, in research laboratories and in academic institutions for the simultaneous determination of multiple active ingredient components in fixed combinations.

Claims

[1] A third derivative zero-crossing UV spectrophotometer configured for the simultaneous determination of vildagliptin and metformin in combined tablet form, consisting of an ultraviolet optical measurement system, a digital signal processor and a software module for derivative calculation. [2] Device according to claim 1, wherein the system operates in third derivative mode with zero-crossing wavelengths set to about 217 nm for vildagliptin and about 230 nm for metformin, thereby enabling selective quantification of both analytes without spectral interference. [3] Device according to claim 1, wherein the analysis software includes an integrated calibration and validation interface for determining linearity, accuracy and recovery in accordance with the standards of the International Council for Harmonization (ICH) and ensures correlation coefficients of over 0.

998. [4] Device according to any of the preceding claims, wherein the system is configured to provide recovery rates between 99 and 100%, precision within a relative standard deviation of ±2% and compatibility with aqueous solvent systems for cost-effective and environmentally friendly pharmaceutical analysis.