Design of Experiments for Critical Material Attributes Assessment of Linagliptin and Metformin Fixed-dose Combination Tablets

Aim of work: This study aimed to determine the amount of excipients in the critical material attributes of linagliptin and metformin sustained release (SR) fixed-dose combination (FDC) tablets using design of experiments (DoE). Methods: A 2³ full factorial design with three center points was performed. For the screening of excipients, 3-factor responses (mannitol, sodium starch glycolate and pregelatinized starch for linagliptin; hydroxypropyl methylcellulose, sodium carboxymethyl cellulose (CMC) and hydroxypropyl cellulose for metformin), 2-levels and 1-center (n=3) point with three responses (friability, assay and dissolution) were applied to the DoE batch using Design-Expert. Results: Most excipients were an important factor in the friability, assay and dissolution results (P<0.05). In the screening of excipients, mannitol (40-60 mg) and pregelatinized starch (40-60 mg) with sodium starch glycolate (5 mg) for linagliptin and hydroxypropyl cellulose (15-23 mg) and CMC (40-55 mg) with hydroxypropyl methylcellulose (260 mg) for metformin were optimal. Conclusion: In summary, selection for the amount of excipients can be defined through levels of risk based on three responses. It can be concluded that the ranges of excipients leading to high quality (low friability and optimal ranges of assay and dissolution) for the screening of excipients were successfully observed by the DoE approach.