An investigation of Granulation Techniques Evaluates Flow Behaviour, Friability and Drug Release of Metformin Hydrochloride

Abstract

Metformin Hydrochloride (MET) is a BCS class III poorly compressible drug. Poor compressibility and poor flow properties of MET highly affects tabletting behaviour. Usually, capping and softness have been observed during the tabletting of MET, reducing manufacturing ease. The study was designed to screen various granulation techniques to evaluate flow behaviour, compressibility, friability, and MET drug release. MET and the binders such as Polyvinylpyrrolidone (PVP) K29/32, PVP K90, and Hydroxypropyl methylcellulose (HPMC) E5 were used in ratio 95:5 for granulation. Granules were prepared by five different granulation techniques such as low shear granulation (LSG), extrusion spheronization (ES), high shear granulation (HSG), fluid bed granulation (FBG), and hot melt granulation (HMG) techniques. Prepared granules were evaluated for the particle size analysis, friability and flow properties. Scanning electron microscopy was employed to study the external morphology of granules. Differential scanning calorimetry (DSC) technique was used to determine the nature of the granules. Further, granules were directly compressed into the tablets by using a rotary tablet press. Tablet hardness, moisture content, dissolution study, and stability study have been conducted. Granules prepared from ES and FBG had confirmed excellent flow.  Tablet prepared from ES, FMG and HMG have assured hardness, moisture content, dissolution, and stability data within acceptable limits. HMG method revealed a successful conversion of crystalline structure into an amorphous form. In-vitro dissolution study has shown that tablets prepared from the HMG method have achieved complete release in 30 min, followed by FBG and ES tablets. HPMC E5, PVP K90 binders were better than PVP K29/32, imparting Strength to the MET granules. HMG and FBG were better techniques that produced free-flowing granules with less friability and drug release.

Keywords- Granulation; Metformin hydrochloride; Binder; Fluid; Melt.