Track: Formulation and Delivery - Chemical - Formulation - Oral - Immediate Release
Category: Poster Abstract
Scale-Up and Stability of Ibuprofen Tablets Containing StarTab®, Directly Compressible Starch
Purpose: Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) commonly used in high doses to treat pain and fever. It is a poorly compressible and poorly flowing material with a low melting point (~75°C) which could lead to punch sticking and picking issues during scale-up at high tableting speeds. Stability issues such as prolonged disintegration times and reduced dissolution rates may also arise. The purpose of this study was to investigate a simple direct compression formulation of ibuprofen using StarTab®, directly compressible starch, on small and large scale tablet compression machines, followed by film coating and stability study. Methods: Immediate release tablets containing ibuprofen (ibuprofen 70, BASF) were formulated at a high dose (200 mg per tablet, 50% w/w) with StarTab (49% w/w) as the filler excipient. The formulation was lubricated with 1% w/w stearic acid. The blend was evaluated for powder flow properties (i.e. bulk/tapped density and flow rate via Flodex). Tablets (target weight 400 mg) were prepared on both small (Piccola 4 station, at speed of 50 rpm) and large scale (Manesty 25 station, at speed of 92 rpm) rotary tablet presses. Tablets were evaluated for physical properties and the batch from large scale trial compressed at 12 kN compression force was film coated using Opadry® QX brown at standard coating parameters in a 24” pan O’Hara coater (Labcoat II). Dissolution testing of coated and uncoated tablets were performed using USP Apparatus II (paddles) at 50 rpm in 900mL of phosphate buffer pH 7.2 at 37°C. The samples were analyzed spectrophotometrically at a UV wavelength of 223 nm. Tablet samples were placed into accelerated storage conditions (40°C/75% RH) and their properties were evaluated through six months. Results: The high dose ibuprofen formulation had acceptable powder flow and compression properties for both small and large scale tableting operations. Scale of manufacture and use of pre-compression did not have an impact on tablet properties. Drug release profile of uncoated tablets prepared on the large scale was consistent with the small scale data (Figure 1). Tablets were successfully coated and free of visible defects. Both uncoated and coated tablets were stable after six months of storage in accelerated conditions at 40°C/75% RH. Conclusion: A simple immediate release ibuprofen formulation was successfully developed using a single tableting excipient (StarTab) with desired performance attributes. The use of StarTab improved powder flow and eliminated the need for superdisintegrant or glidant in the formulation. The resulting tablets were robust with fast disintegration times and were film coated without any visible defects. Ibuprofen tablets were stable through six months of accelerated conditions with no change in their physical properties or drug release profiles.