Continuous manufacturing of immediate release (IR) tablets by Hot-Melt Extrusion (HME) and injection molding (IM) techniques

Purpose To evaluate hot melt extrusion (HME) and injection molding (IM) for the continuous manufacturing of IR tablets. Methods Polymeric fillers were mixed with plasticizers and functional adjuvants and/or a model drug were in some cases added to the formulation. HME was performed in a single-screw extruder (Extrusiograph 19/25D, Brabender, D); tablets were obtained by cutting with a bench-top saw cylindrical products (h 4 mm) extruded using a rod-shaped (ø 8 mm) die. IM was performed in a micromolding machine (BabyPlast 6/10P, Cronoplast S.L.; Rambaldi S.r.l., I); tablets were obtained with a cylindrical (ø 8 mm, h 4 mm) mold. Disk-shaped screening items (ø 30 mm, h 1 mm) were also prepared, by cutting 1 mm thick extruded sheets or by molding with a specific mold. Products were checked for weight, thickness and mass loss in the dissolution and disintegration apparatus. The dissolution rate from drug-containing tablets was also evaluated. Results Thermoplastic polymers were evaluated as tablet fillers based on their processability and on the mass loss behavior of molded disks. Soluble polymers employed for the preparation of solid dispersions by HME or for the conventional coating of tablets and traditional fillers, such as starch, were considered. Starch-derived disintegrants were also taken into account as they have shown a thermoplastic behavior and demonstrated to maintain the potential for disintegration after processing. All polymers could be processed with no need for technological aids except for a plasticizer. Hydroxypropylcellulose (HPC)- and sodium starch glycolate (EXPCLV)-based formulations were selected for investigating the influence of a poorly-soluble model drug and of functional aids able to affect the disintegration and dissolution rate. EXPCLV-based tablets showed the most promising results, thanks to the intrinsic ability of the polymeric filler to disintegrate. The addition of soluble (e.g. sodium chloride and Kollicoat® IR), disintegrant (Explotab® and AcdiSol®) or effervescent adjuvants was demonstrated a successful strategy for the improvement of the dissolution rate. Conclusion The feasibility of IR tablets by HME and IM was demonstrated. Promising results in terms of suitable polymeric fillers and formulation strategies for promoting tablet disintegration and drug dissolution were obtained.