Continuous melt granulation to develop high drug loaded sustained release tablet of Metformin HCl

The present work explores the application of melt granulation technology to develop a high drug loaded sustained release matrix tablet of Metformin HCl using hydroxypropylcellulose (HPC) as a hydrophilic binder and stearic acid as an extrusion aid for producing cohesive granules. This novel approach allowed the use of a minimum number of excipients to reduce the tablet size, and to enhance compressibility of the drug. This also offered a cost effective method owing to the elimination of a 'drying step' prevalent in wet granulation method. Moreover, this research also focuses on resolving the processability issues associated with the use of HPC Nisso-H at high drug loading. The thermal lubricants were screened for this purpose and evaluated for their impact on extrudability, granule and tablet characteristics. Stearic acid was selected as the thermal lubricant, which not only contributed to the inhibition of burst release, but also improved the flow property of the granules.The developed matrix tablet (75% drug loading) resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug. Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose, highly water soluble drug otherwise difficult to process using standard batch-granulation.

Graphical Abstract108