Risk based approach for design and optimization of novel tablet for type-II diabetes

Vaishali Thakkar, Hardeep Mahida, Lalji Baldaniya, Mukesh Gohel, Tejal Gandhi, Hitesh Raval, Nirav Patel


Objective: The main focus of current investigation was to develop and optimize the manufacturing process of novel tablet containing sustained release Metformin HCl (MET) in core and immediate release Glimepiride (GLIMP) in coating for type II diabetes, by risk assessment approach using Failure Mode Effect Analysis (FMEA) tool.

Methods: Quality risk management (QRM) studies were conducted for each critical process parameters of active coated tablet of MET and GLIMP. A 32 full factorial design was employed for optimization of core tablet of MET to investigate effect of amount of HPMC K100M (A) and HPMC K15M (B) on percent drug release up to 10 hr. GLIMP coating was done on optimize core tablet. A 23 factorial design was used for optimization of coating to investigate the effect of spray rate, inlet air temp., and pan speed on coating parameter. Main effects and interaction plots were generated to study effects of variables. Amount of HPMC K100M and 15M have risk priority number (RPN) 50 and require through investigation and optimization.

Results: The selection of optimized formulation was done on the basis of overlay contour plots and desirability function. The optimized formulation exhibited percent drug release of 30.61, 54.13 and 96.86 at 1, 3 and 10 hr. respectively. Using design of experiment, the optimized conditions selected for coating are spray rate, temperature, pan speed was 3.34 ml/min, 60.60C and 13.2 RPM respectively. The critical quality attributes of unit operations like blending, compression and coating were optimized. The optimized formulations were stable for three months at accelerated and long term stability conditions.

Conclusions: The developed formulation may provide prudently a better substitute for conventional tablet in circumventing its hiccups; improve biopharmaceutical properties, providing sustained and immediate release and may anticipate a better bioavailability and patient compliance


Risk based approach, Metformine hydrochloride, Glimepiride, Type II diabetes, Quality target product profile, Critical quality attributes, Risk assessment

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http://www.who.int/topics/diabetes_mellitus /en/

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