Formulation development and in-vitro comparative study of extended-release paracetamol tablets

Abstract

This study focuses on developing simple, robust methods to prepare extended release paracetamol 665 mg hydrophilic matrix tablets using hydroxypropyl methylcellulose (HPMC) as the principal matrix former and binder in a wet granulation process. Nonionic cellulose ethers such as HPMC are widely used in oral extended release systems because they hydrate to form a viscous gel layer that controls drug diffusion and matrix erosion, thereby sustaining drug release over an extended period. In this work, paracetamol–HPMC matrix tablets were produced by wet granulation using water as the granulating fluid, providing a solvent free, industry relevant manufacturing approach. Two granule populations were designed: “fast release” granules containing the super disintegrant croscarmellose sodium, and “slow release” granules without disintegrant to enhance gel formation and retard release. These granules were blended at different ratios before compression on a tablet press to obtain biphasic and sustained release profiles tailored to match existing modified release paracetamol products. The optimized formulation was benchmarked against leading extended release paracetamol brands marketed in the USA and Europe by comparing 12 hours dissolution profiles, which demonstrated that the in vitro drug release behavior of the developed tablets was comparable to that of the reference products, indicating their potential as cost effective alternatives in the kingdom of Saudi Arabia.