Context: Niacin (vitamin B3) is a micronized active pharmaceutical ingredient (API) with poor flow properties making the production of high-dose sustained-release tablets by direct compression a challenge.
Objective: We evaluated various wet granulation processes as a simple and efficient approach to obtain high-dose (500 and 1000 mg) niacin sustained-release lipid matrix tablets.
Materials and methods: A high melting-point lipid (Compritol® 888 ATO) was used as the sustained-release agent. Tablets were prepared by various wet granulation techniques, with different process parameters and binder concentrations to identify the optimal process conditions.
Results: A binder (PVP) was needed to increase particle bonding and tablet strength. Process parameters, such as spray rate and quantity of liquid, had only a slight impact on the properties of the granules and resultant tablets, in the presence of low binder concentrations. Increasing binder concentration improved granule wetting, resulting in significant granule growth and improved flow properties. Sustained-release over 12 h was observed for all the compacted granules, irrespective of the drug dose. The sustained-release kinetics for 1000 mg niacin matrix tablets with Compritol 888 produced with the identified optimal parameters were similar to those for the market reference product, Niaspan® FCT 1000 mg. The tablets were stable for up to six months when stored at 25 and 40 °C.
Conclusions: Wet granulation with Compritol 888 presents an effective approach to improve material flow and compressibility. High-dose lipid matrix tablets with sustained release profiles can be successfully produced.
Keywords: Glyceryl behenate; Niaspan FCT; lipid matrix tablets; niacin; process optimization; vitamin B3; wet granulation.