Abstract

Three granulation processing methods; Hot melt extrusion (HME), Roller compaction Dry granulation (RCDG) and Moisture assisted dry granulation (MADG) are assessed to evaluate different polymeric binders for preparation of a high dose immediate release tablet of acetaminophen drug. Different characterization techniques were used to enumerate poor physical property characteristic for drug (paracetamol) including hygroscopicity, low solubility and bulk density, and poor powder flowability. In case of maltodextrin all techniques produce uniform granules while, HPC produce more fine particles. A massive enhancement in drug loading of 8.5:1.5 was achieved via hot melt extrusion process using low molecular weight polymeric-binders as PVP K12, HPC SSL and Maltodextrin. Granules produced by melt processing contained less fines as compared to MADG and RCDG. A formulation and process for dry granulation by roller compaction was also developed. Particle size distributions of milled ribbons were analysed by sieve analysis. Higher density granules produced with roll force of 15 kN/cm and improved flow properties and less fines content (<75 μm) was observed. Drug loading (API:excipient ratio) in roller compaction was 8:2. IR formulation of acetaminophen was developed using MADG process and characterised for granular and tableting properties. Acceptable content uniformity, dissolution results were obtained using MADG and HME. While RCDG gives poor content uniformity tesults. Differential Scanning Calorimetry analysis suggested the amorphisation of the drug in the HME granules containing the three excipients. This result was then confirmed by X-ray powder diffraction analysis, hence higher dissolution rate for HME granules than RC and MADG granules. Both HME and MADG are viable granulation process choices for scale up to overcome the physical property limitations of Acetaminophen drug.