Abstract
A novel, stability indicating, reverse phase high-performance liquid chromatography (RP-HPLC) method was developed to determine the S-isomer of linagliptin (LGP) in linagliptin and metformin hydrochloride (MET HCl) tablets (LGP–MET HCl) by implementing design of experiment (DoE), i.e., two-level, full factorial design (23 + 3 centre points = 11 experiments) to understand the critical method parameters (CMP) and its relation with the critical method attribute (CMA), and to ensure robustness of the method. The separation of the S-isomer, LGP and MET HCl in the presence of their impurities was achieved on Chiralpak® IA-3 (Amylose tris (3, 5-dimethylphenylcarbamate), immobilized on 3 µm silica gel) stationary phase (250 × 4.6 mm, 3 µm) using isocratic elution and detector wavelength at 225 nm with a flow rate of 0.5 mL·min−1, an injection volume of 10 µL with a sample cooler (5 °C) and column oven temperature of 25 °C. Ethanol:Methanol:Monoethanolamine (EtOH:MeOH:MEA) in the ratio of 60:40:0.2 v/v/v was used as a mobile phase. The developed method was validated in accordance with international council for harmonisation (ICH) guidelines and was applied for the estimation of the S-isomer of LGP in LGP–MET HCl tablets. The same method also can be extended for the estimation of the S-isomer in LGP dosage forms.
Highlights
Linagliptin (LGP) is a class of DPP-4 (Dipeptidyl peptidase-4) inhibitor with a unique pharmacokinetic (PK) profile, characterized by negligible renal excretion, and used in the treatment of type II diabetes as glucagon increases blood glucose levels, while DPP-4 inhibitors reduce glucagon and blood glucose levels
Metformin hydrochloride (MET HCl) is an oral antidiabetic drug in the biguanide class. It is used for the treatment of type II diabetes, in overweight and obese people and those with normal kidney function
Classical insulin secretagogues include sulfonylureas [7], but these glucose-lowering agents implicate a risk of exposure to potentially severe hypoglycaemia [8,9,10,11] weight gain [8,9,11,12,13] and PK interactions [14], which may worsen outcomes [15]
Summary
Linagliptin (LGP) is a class of DPP-4 (Dipeptidyl peptidase-4) inhibitor with a unique pharmacokinetic (PK) profile, characterized by negligible renal excretion, and used in the treatment of type II diabetes as glucagon increases blood glucose levels, while DPP-4 inhibitors reduce glucagon and blood glucose levels. Metformin hydrochloride (MET HCl) is an oral antidiabetic drug in the biguanide class. It is used for the treatment of type II diabetes, in overweight and obese people and those with normal kidney function. LGP and MET HCl are not prone to PK drug–drug interactions. Their co-administration improves blood glucose control more potently than either compound separately, without hypoglycaemia and without increasing metformin related gastrointestinal side effects. A combination of LGP and MET HCl is very effective to control type II diabetes [16]
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