Category: Formulation and Quality
Purpose: This study was conducted to show the effect of binder choice in twin-screw granulation of a poorly compactable API (metformin hydrochloride). The resulting granules and tablets were evaluated and compared.
Methods: 94 % metformin hydrochloride (Auro Laboratories Ltd, India) was used as a model drug. 5 % of hydroxypropyl cellulose grades SSL, SSL SFP, SL FP and L FP (Nippon soda, Japan), copovidone (PVP/VA Kollidon VA-64) and povidone (PVP Kollidon K-30, BASF, Germany) were used as binder and 1 % magnesium stearate (Wako pure chemistry, Japan) as a lubricant. To avoid agglomeration, the drug was preliminary milled by power mill (P-200, Dalton, Japan). The granulation process was performed by using 11 mm twin-screw extruder (Process 11, Thermofisher, Germany) at 30 °C, 200 rpm screw speed and 15 g/min powder feed. Compressibility of granules was evaluated by powder rheometer (FT-4 Freeman Technology, England). The resulting granules were compressed on rotary press (VELA 5, Kikusui Seisakujo, Japan) to produce round-faced, 13 mm, 600 mg tablets. The dissolution tests were carried out in 2nd fluid using USP II paddle method.
Results: Regardless of the binder used, the resulting granules demonstrated a bi-modal particle size distribution with average particle size (D50) of 250 mm. Powder flow of the granules was similar, regardless of binder. Compactability of the HPC-based granules was much better compared to povidone and copovidone granules (Figure 1). The highest tablet breaking forces were achieved with HPC-SSL SFP followed by the other HPC grades. Povidone and copovidone granulations exhibited lower compactability and also revealed capping, and breaking force reduction at high compaction forces. (Figure 1). All the tablets released 75 % of the drug in 15 min (Figure 2). HPC-SSL SFP demonstrated similar dissolution profile with povidone and copovidone (Figure 2).
Conclusion: Micronized HPC-SSL SFP demonstrated the best performance as a binder in twin-screw extrusion of high dose metformin hydrochloride compared to PVP K-30, copovidone and other grades HPC. The excellent compactability of the granules without signs of capping or lamination as well as the fast drug dissolution makes SSL SFP a preferable binder for extrusion granulation and related continuous manufacturing technologies.