A Novel Solvent System to Prepare Pellets of Active Pharmaceutical Ingredients Having Tacky Wet-Mass Forming Propensity By Extrusion Spheronization Technique

Itopride hydrochloride (IH) is a prokinetic agent that has been widely used for the treatment of dyspepsia and other gastrointestinal conditions. Because of its short biological half-life, it is suitable candidate for sustained drug delivery systems. However, IH has propensity to form a tacky/sticky wet-mass when comes in contact with water, especially in presence of hydroxypropyl methyl cellulose (Hypromellose). This makes it extremely difficult to process IH into sustained release granules or pellets using hypromellose as a matrix-forming material and aqueous-based solvent system. Therefore, aim of this study was to explore an optimum solvent system that can produce discrete and spherical SR pellets of IH by extrusion spheronization technique. Various conventional and non-conventional solvent systems were evaluated, and it was found that water: PEG 400 system has potential to produce a non-tacky wet mass of IH in presence of other pharmaceutical excipients. Therefore, IH and excipients were mixed and granulated using purified water: PEG 400 (85:15 ratio) in a high shear granulator. The wet mass was extruded using screw extruder equipped with 1.0 mm screen. The extrudes were spheronized at 700 ± 100 rpm for 10 min and dried in fluid bed drier at a target bed temperature of 42°C. Pellets were characterized for morphology, particle size, friability, flow property and dissolution (pellets filled in capsule). Results revealed that the purified water: PEG 400 (85:15 ratio) system can produce a non-tacky wet-mass of IH and pharmaceutical excipients including hypromellose, which can be processed successfully into discrete and spherical pellets with sustained release profile and satisfactory pharmacotechnical properties.