Background: Heart attack predominantly occurs during the last phase of sleep and early
morning hours, causing millions of death worldwide. Hydrochlorothiazide (HCTZ) is a recommended
drug for the prevention of heart disease, but its long action (>4 h) dosage form is lacking in
the commercial market and development of modified-release formulation may have industrial significance.
Regulatory agencies emphasize Quality by Design based approach for product development
to entrust quality in the product.
Objective: The current research aimed to develop a quality product profile of HCTZ modifiedrelease
tablets (MRT; ~14 h) by applying Response Surface Methodology using the computational
Methods: Three independent factors were identified by qualitative and quantitative risk assessment.
Statistical terms like p-value, lack of fit, the sum of square, R-squared value, model F value, and
linear equations were determined. Graphical tools like normal plot of residual, residual vs predicted
plot and box cox plot were used to verify the model selection. The graphical relationship among the
critical, independent variables was represented using the Contour plot and 3-D surface plot. Design
space was identified by designing an overlay plot using response surface design.
Results: Excellent correlation was observed between actual and predicted values. Similarity Factor
(F2) of reproducible trials was 78 and 79, and content uniformity was 100.9% and 100.4%. Average
weight, hardness, thickness, diameter, and friability were within acceptable limits.
Conclusion: QbD approach, along with a quality risk management tool, provided an efficient and
effective paradigm to build quality MRT of HCTZ.