Design of Experiments as a Tool for the Optimization of a Fixed-Dose Combination: A Case Study Focused on Formulation

November 20, 2025

Cardiovascular diseases are a leading cause of morbidity and mortality worldwide, reinforcing the need for effective therapies and pharmacological regimens that promote patient adherence. Fixed combination medicinal products (FCMP) products have gained importance in this field because they allow the combination of different drugs in a single dosage form, reducing the number of daily administrations and increasing treatment adherence. This study aimed to optimize a tablet formulation containing two active pharmaceutical ingredients, using an approach based on the principles of Experimental Design. The study focused on optimizing the external phase of the formulation to evaluate the effect of microcrystalline cellulose (MCC), colloidal silicon dioxide (CSD) and magnesium stearate (MgSt) on the mixture's flow parameters. Statistical analysis identified the main effects and interactions between the factors studied. The results demonstrated that CSD significantly improved flow, while MCC and MgSt slightly increased blend cohesiveness. The model proposed an optimized formulation (10.54% MCC, 0.95% CSD, and 1.25% MgSt), which was experimentally confirmed with agreement between predicted and observed values. The formulation exhibited good flow and compressibility properties, resulting in tablets with low friability, adequate hardness, and disintegration time within pharmacopeial limits. Overall, the results demonstrated the effectiveness of the experimental model in optimizing the formulation, highlighting the importance of controlling critical blending parameters to obtain tablets with adequate physical performance.

Authors in the community:

• 

  G

  Gonçalo Silveirinha Caldeira

  ist1111010

Supervisors of this institution:

• 

  A

  Ana Catarina Beco Pinto Reis

  ist430358

industrial-biotechnology - Industrial Biotechnology

eng - English

Instituto Superior Técnico