A Review on Development and Validation for the Simultaneous Estimation of Lansoprazole and Domperidone in Bulk and Capsule Dosage Form

Abstract

Lansoprazole is an effective proton pump inhibitor utilized for managing various acid-related disorders, such as ulcers and gastroesophageal reflux disease (GERD), by significantly reducing stomach acid production. It has demonstrated a general tolerance among users, with common side effects including headaches, nausea, and diarrhea, while serious side effects are comparatively rare. Importantly, lansoprazole may provide superior healing results for conditions like ulcers and esophagitis compared to alternative medications such as ranitidine. Furthermore, it plays a key role in eradicating Helicobacter pylori bacteria when used in combination with antibiotics. Domperidone is a dopamine antagonist primarily used to treat nausea, vomiting, and gastrointestinal motility disorders. It functions both as an antiemetic, alleviating symptoms of nausea and vomiting, and as a prokinetic agent, enhancing gastric emptying. Notably, it is regarded as safer compared to metoclopramide due to its limited ability to cross the blood-brain barrier, thus minimizing central nervous system side effects. However, its safety profile is under scrutiny, particularly concerning potential cardiac effects and its impact on mental health during lactation. The future scope for the simultaneous estimation of Lansoprazole (LAN) and Domperidone (DOM) emphasizes the development of efficient, sustainable, and high-throughput analytical methods. Key areas of focus include minimizing hazardous solvent use through green chemistry principles, potentially utilizing supercritical fluid chromatography (SFC) or aqueous- based mobile phases in reverse-phase high-performance liquid chromatography (RP-HPLC). Research is anticipated to concentrate on ultra-high performance liquid chromatography (UHPLC) and chip-based microfluidic systems, offering faster analysis and reduced solvent consumption compared to traditional HPLC. There is a trend towards integrating analytical methods to enhance specificity and sensitivity, such as liquid chromatography-mass spectrometry (LC-MS/MS) for trace analysis, pharmacokinetic studies, and impurity profiling essential for regulations. The development of automated sample preparation and analysis systems aims to boost efficiency in quality control during manufacturing. Additionally, the use of chemometrics and multivariate calibration methods, including Partial Least Squares (PLS) and Principal Component Regression (PCR), alongside UV-spectrophotometry is expanding to improve accuracy and reduce analysis times, particularly in complex samples. Emphasis is also placed on creating robust methods that can accurately differentiate and quantify active pharmaceuticals from degradation products under various stress conditions, including acidic, basic, thermal, oxidative, and photolytic environments. Future methods will require thorough validation according to the International Conference on Harmonization (ICH) guidelines regarding accuracy, precision, linearity, specificity, limits of detection (LOD), limit of quantification (LOQ), and robustness, ensuring compliance with major regulatory bodies like the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Future validation strategies may also incorporate real-time release testing (RTRT) principles for in-line or online process monitoring, advancing beyond conventional post-manufacturing testing. In conclusion, the trajectory is towards more sophisticated, rapid, environmentally friendly, and highly specific analytical methods that adhere to rigorous global regulatory standards.

Introduction

Lansoprazole is a proton pump inhibitor widely used to treat acid-related disorders such as ulcers, GERD, and Zollinger-Ellison syndrome by reducing stomach acid. It is generally well-tolerated, with mild side effects like headache, nausea, and diarrhea. Lansoprazole is particularly effective in ulcer healing, esophagitis treatment, and H. pylori eradication when combined with antibiotics. Long-term use may affect nutrient absorption (folic acid and vitamin B12), requiring supplementation.

Domperidone is a peripheral dopamine antagonist used as an antiemetic and prokinetic agent to enhance gastrointestinal motility and alleviate nausea and vomiting. It is considered safer than metoclopramide regarding central nervous system side effects but may pose cardiac risks (e.g., prolonged QT interval) and potential mental health effects. Its use is regulated in certain countries due to these concerns.

Analytical Methods for Simultaneous Estimation:

• UV–Vis spectroscopy, RP-HPLC, and spectrophotometric techniques have been developed to simultaneously quantify lansoprazole, domperidone, and related drugs in bulk and dosage forms.

• Signal processing methods like continuous wavelet transform (CWT) and derivative spectroscopy resolve overlapping spectra effectively.

• RP-HPLC methods have been optimized for greenness, accuracy, precision, robustness, and cost-effectiveness, often validated per ICH guidelines.

• Bilayer tablet formulations combining domperidone with gastroretentive agents (e.g., itopride) demonstrate controlled, optimized release for enhanced therapeutic efficacy.

• Stability-indicating methods for stress degradation studies and quality control are widely reported, ensuring safe and effective drug delivery.

Future Scope:

• Emphasis on green chemistry, using aqueous mobile phases, supercritical fluid chromatography, and microfluidic or UHPLC systems.

• Integration of LC-MS/MS for trace analysis, impurity profiling, and pharmacokinetic studies.

• Automation of sample preparation and chemometric techniques (PLS, PCR) to improve throughput and accuracy.

• Robust methods for separating active drugs from degradation products under various stress conditions, with rigorous ICH-compliant validation.

• Implementation of real-time release testing (RTRT) and Quality by Design (QbD) frameworks to streamline manufacturing and quality control.

Conclusion

In conclusion, the future trajectory is towards more sophisticated, rapid, environmentally friendly, and highly specific analytical methods that comply with rigorous global regulatory standards.

References

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Copyright

Copyright © 2025 Kiran V. Vyavhare, Aijaz A. Sheikh, K. R. Biyani. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.