Roorkee College of Pharmacy Roorkee
The design and development of Dexlansoprazole (DEX) Lansoprazole pellets require a meticulous approach to ensure the final product meets the stringent standards of quality, efficacy, and safety. In this context, Quality Management System (QMS) and Quality by Design (QbD) play pivotal roles. QMS provides a structured framework that ensures compliance with regulatory requirements, facilitates traceability, and promotes continuous improvement throughout the product lifecycle. It emphasizes risk management, ensuring that potential issues are identified early, and corrective actions are implemented proactively. In parallel, QbD focuses on building quality into the product from the outset. It involves identifying critical quality attributes (CQAs), understanding the relationship between formulation variables and product performance, and applying Design of Experiments (DoE) to optimize the formulation and manufacturing processes. By integrating QMS and QbD, the development of DEX Lansoprazole pellets benefits from enhanced product consistency, minimized variability, and a robust control strategy. This integrated approach not only ensures the desired release profile, stability, and patient compliance but also streamlines the development process, reduces risks, and improves the overall quality of the final product. Together, QMS and QbD contribute to the creation of a reliable and effective therapeutic product that meets the highest pharmaceutical standards.
The design and development of Dexlansoprazole (DEX) Lansoprazole pellets require a comprehensive and structured approach to ensure the formulation is effective, consistent, and meets regulatory standards. Dexlansoprazole, a proton pump inhibitor (PPI), has a complex pharmacokinetic profile, and the development of a pellet dosage form offers significant advantages in terms of controlled and sustained drug release, improved patient compliance, and enhanced bioavailability. However, the challenges associated with formulating DEX in a pellet form—such as stability, drug release characteristics, and manufacturing scalability—necessitate a careful and systematic development process. Quality Management Systems (QMS) and Quality by Design (QbD) are critical frameworks that guide the development of pharmaceutical products, including DEX Lansoprazole pellets. QMS focuses on ensuring consistent quality through structured processes, documentation, and regulatory compliance, while QbD emphasizes designing quality into the product from the outset, focusing on identifying critical quality attributes (CQAs), understanding the relationship between process parameters and product performance, and ensuring the product meets its desired therapeutic outcomes. The integration of QMS and QbD throughout the DEX Lansoprazole pellets' lifecycle enhances product development by ensuring the final product is robust, reproducible, and meets predefined quality standards. QMS helps mitigate risks through documentation, process controls, and continuous monitoring, while QbD facilitates optimized formulation development through risk-based design, real-time monitoring, and efficient process control strategies. This paper aims to explore the roles of QMS and QbD in the design and development of DEX Lansoprazole pellets, highlighting how their integration ensures high-quality, patient-centric, and regulatory-compliant pharmaceutical products.
Overview of Dexlansoprazole Pellets [6-12]
Dexlansoprazole is the R-enantiomer of lansoprazole, a proton pump inhibitor (PPI) that provides effective management of acid-related disorders such as gastroesophageal reflux disease (GERD) and erosive esophagitis. It is uniquely formulated using a dual delayed-release (DDR) delivery system, which enables two distinct drug release phases in the gastrointestinal (GI) tract, resulting in extended plasma drug levels and prolonged therapeutic action.
Advantages of Pellet-Based Formulation
The pellet-based multiparticulate delivery system used in Dexlansoprazole capsules offers several critical advantages over conventional dosage forms:
Typical Pellet Formulation Components
The formulation of Dexlansoprazole pellets consists of a multiparticulate system with multiple coating layers to achieve site-specific release:
Quality Management System (QMS): A Framework for Compliance [13-15]
A Quality Management System (QMS) is a structured framework that encompasses the policies, processes, standard operating procedures (SOPs), and resources required to ensure consistent product quality, safety, and regulatory compliance in pharmaceutical manufacturing. The primary objective of a QMS is to ensure that pharmaceutical products are manufactured under controlled conditions that meet predefined quality standards.
Key components of a pharmaceutical QMS include:
A robust QMS is designed to be proactive rather than reactive and is aligned with internationally recognized standards and guidelines. Notably:
Together, these frameworks foster a culture of continuous improvement, facilitate regulatory readiness, and support compliance with global Good Manufacturing Practice (GMP) regulations.
Quality by Design (QbD): Scientific Approach to Development [16-20]
Quality by Design (QbD) is a modern, science- and risk-based approach to pharmaceutical development, as outlined in the ICH Q8(R2) guideline. It emphasizes building quality into the product from the outset, rather than relying solely on end-product testing. QbD promotes process understanding, identification of critical variables, and control strategies that ensure consistent product quality throughout the lifecycle.
According to ICH Q8(R2), the essential elements of QbD include:
This structured approach is especially valuable in the development of complex oral dosage forms, such as delayed-release pellets of Dexlansoprazole, where formulation and process variables significantly affect drug performance.
The QTPP serves as the foundation of product design and outlines the desired quality characteristics to ensure safety and efficacy.
|
Attribute |
Target |
|
Dosage form |
Delayed-release pellets |
|
Strength |
30 mg, 60 mg |
|
Release profile |
Dual pulse release |
|
Stability |
Acid resistance, thermal stability |
These targets inform the identification of Critical Quality Attributes (CQAs) and guide formulation and process development.
CQAs are physical, chemical, biological, or microbiological properties that must be controlled within predefined limits to ensure product quality.
CPPs are variables in the manufacturing process that have a direct impact on the identified CQAs. These must be carefully controlled and monitored.
Risk assessment tools like Failure Mode and Effects Analysis (FMEA) or Ishikawa diagrams are used to link CPPs with CQAs and determine control strategies accordingly
Risk Assessment and Design Space [21-28]
Risk assessment tools like FMEA and Ishikawa diagrams help identify high-risk parameters. Design space is then developed using DoE (Design of Experiments) techniques.
Example:
Control Strategy
A comprehensive control strategy includes:
Regulatory Perspectives
Regulatory agencies support QbD submission through:
The FDA’s QbD pilot program and EMA’s scientific advice framework have both encouraged QbD adoption for complex formulations like Dexlansoprazole pellets.
Integration of QMS and QbD: Synergies and Benefits
Case Study: Hypothetical Application
A development project for Dexlansoprazole pellets using QbD resulted in:
These outcomes were supported by a fully compliant QMS ensuring robust documentation and quality oversight.
Challenges and Future Directions
Future directions include:
CONCLUSION
The integration of Quality Management Systems (QMS) and Quality by Design (QbD) in the development of Dexlansoprazole delayed-release pellets represents a transformative approach in pharmaceutical manufacturing. By embedding quality into every stage of the product lifecycle—from formulation design to commercial production—this dual framework ensures that the final product consistently meets predefined standards of safety, efficacy, and performance. QMS provides the procedural backbone to maintain compliance, manage risks, and drive continuous improvement, while QbD offers a scientific foundation for understanding critical material attributes (CMAs) and critical process parameters (CPPs) that influence critical quality attributes (CQAs). Together, they facilitate robust process design, reduce variability, enhance manufacturing efficiency, and support regulatory flexibility through comprehensive product knowledge. This paradigm shift—from quality-by-testing to quality-by-design—is essential for modern pharmaceutical development, especially in the context of complex dosage forms like dual delayed-release pellets. It not only ensures regulatory compliance aligned with ICH and ISO guidelines but also promotes innovation, product consistency, and patient-centric outcomes.
REFERENCES
Shazuddin Shamsi*, Dr. Amit Chaudhary, Integrating Quality Management Systems (QMS) and Quality by Design (QBD) in the Design and Development of Dexlansoprazole Pellets: Enhancing Product Quality, Consistency, and Regulatory Compliance, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 1054-1060. https://doi.org/10.5281/zenodo.15353202
10.5281/zenodo.15353202
