Employment of Quality by Design Approach via Response Surface Methodology to Optimize and Develop Modified-release...

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Quality by Design (QbD)

Background:

• Heart attacks often occur in the early morning, necessitating effective preventative medications.
• A long-acting formulation of hydrochlorothiazide (HCTZ) is needed, as current options have short durations of action.
• Regulatory bodies advocate for Quality by Design (QbD) in pharmaceutical development to ensure product quality.

Purpose of the Study:

• To develop a quality product profile for hydrochlorothiazide modified-release tablets (MRT) with a ~14-hour release profile.
• To apply Response Surface Methodology (RSM) and computational QbD for formulation development.
• To establish a robust manufacturing process for HCTZ MRT.

Main Methods:

• Risk assessment was used to identify critical factors influencing the HCTZ MRT.
• Response Surface Methodology (RSM) and statistical analysis (p-value, R-squared) were employed to model the formulation.
• Graphical tools (contour plots, 3-D surface plots, overlay plots) were utilized to define the design space.

Main Results:

• The developed HCTZ MRT demonstrated a release profile of approximately 14 hours.
• Reproducible trials showed high Similarity Factor (F2) values (78 and 79) and excellent content uniformity (100.9%, 100.4%).
• Physical parameters including weight, hardness, thickness, diameter, and friability were within acceptable pharmaceutical limits.

Conclusions:

• The Quality by Design (QbD) approach, integrated with quality risk management, proved effective for developing high-quality HCTZ modified-release tablets.
• This QbD-based strategy ensures the consistent production of a reliable, long-acting HCTZ formulation.
• The study provides a framework for developing other modified-release drug products using QbD principles.