Annales pharmaceutiques francaises · 2025
QbD-based optimisation and level A IVIVC of gliclazide sustained-release matrix tablets using Pectin and HPMC.
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Chinnaiyan Santhosh Kumar, Veedu Anjana Thekke, Rathnakaran Arya, Veedu Devika Karattu, Rayaroth Malavika Panayanthatta, K V Arun Kumar
Аннотация
BACKGROUND: Conventional oral gliclazide (G) therapy in type 2 diabetes mellitus management often resulted to fluctuating blood glucose levels, frequent dosing, and poor patient compliance. The sustained-release matrix tablets (SRMT) offer the potential to steady plasma concentrations, reduce hypoglycemia, and improve patient compliance.
METHODS: A Quality by Design (QbD) approach was applied to optimise GSRMT using Pectin and HPMC as independent formulation variables. A Central composite design (CCD) was employed, evaluating hardness and drug release as critical quality attributes (CQAs). The response surface methodology (RSM) and desirability functions were used for optimisation. The in vivo performance of the optimised formulation (OPF), predicted using the convolution approach, was validated and compared with the marketed formulation (MF). Furthermore, the optimised formulation was characterised using FTIR and SEM analysis.
RESULTS: The OPF was showed a tablet hardness of 4.13kg/cm2, controlled burst release (13.45% at 1h), extended release (93.22% at 12h), and a t50% of 5.31h. The OPF exhibited good excipient compatibility, with sustained drug release by the combined action of erosion and diffusion within the hydrophilic matrix. The pharmacokinetic predictions based on convolution yielded Cmax 1.76μg/mL,Tmax 10h, AUC0-∞ 39.85μg·mL-1·h, closely matching market formulation and literature reported in vivo data. The prediction errors are <10%, validating the Level A-IVIVC model.
CONCLUSION: The QbD directed approach successfully developed a robust GSRMT with predictable in vitro-in vivo performance, offering a cost effective and clinically relevant alternative to conventional formulations.
METHODS: A Quality by Design (QbD) approach was applied to optimise GSRMT using Pectin and HPMC as independent formulation variables. A Central composite design (CCD) was employed, evaluating hardness and drug release as critical quality attributes (CQAs). The response surface methodology (RSM) and desirability functions were used for optimisation. The in vivo performance of the optimised formulation (OPF), predicted using the convolution approach, was validated and compared with the marketed formulation (MF). Furthermore, the optimised formulation was characterised using FTIR and SEM analysis.
RESULTS: The OPF was showed a tablet hardness of 4.13kg/cm2, controlled burst release (13.45% at 1h), extended release (93.22% at 12h), and a t50% of 5.31h. The OPF exhibited good excipient compatibility, with sustained drug release by the combined action of erosion and diffusion within the hydrophilic matrix. The pharmacokinetic predictions based on convolution yielded Cmax 1.76μg/mL,Tmax 10h, AUC0-∞ 39.85μg·mL-1·h, closely matching market formulation and literature reported in vivo data. The prediction errors are <10%, validating the Level A-IVIVC model.
CONCLUSION: The QbD directed approach successfully developed a robust GSRMT with predictable in vitro-in vivo performance, offering a cost effective and clinically relevant alternative to conventional formulations.