Exploratory studies in heat-assisted continuous twin-screw dry granulation: A novel alternative technique to conventional dry granulation.

Dry granulation is the preferred technique for solvent-sensitive products, especially drugs with stability problems such as hydrolysis. Twin-screw granulation is a continuous granulation technique, offering a potential alternative to conventional dry granulation techniques such as roller compaction. The major advantage of twin-screw granulation is the ability to adjust process parameters of dry granulation without compromising the compression properties. This study was aimed to perform exploratory studies of heat-assisted continuous twin-screw dry granulation process to formulate sustained release tablets for APIs with different melting points: theophylline, acetaminophen and lidocaine hydrochloride hydrate. Granulation feasibility was studied with different binders (e.g. Klucel™ EF, Kollidon® VA64), sustained release agents (e.g. Klucel™ MF, Eudragit® RSPO) and diluents at various drug loads. The processing conditions were below the melting point or glass transition temperature of the formulation ingredients. After successful granulation, DSC and XRD studies revealed the crystalline nature of the granules and FTIR studies showed no interaction of the API with the excipients. The granules were compressed into sustained release tablets without any compressibility issues. The tablets were stable after testing for 6 months at 25 °C/60% RH. This novel continuous dry granulation technique may offer an excellent alternative to conventional dry granulation techniques.