Novel disintegrating microcrystalline cellulose pellets with improved drug dissolution performance

Pellets obtained from extrusion/spheronization generally do not disintegrate, especially those prepared from microcrystalline cellulose (MCC). The aim of present study was to develop fast disintegrating MCC pellets in order to improve drug dissolution. Formulations containing a model drug having a low aqueous solubility (i.e., indomethacin) and MCC were prepared with or without the addition of polyethylene glycol 400 (PEG 400; 0–10% w/w), polysorbate 80 (0–10% w/w) and croscarmellose sodium (CCS; 0–10% w/w) using a basket extruder and spheronizer. Ethanolic solution (15% v/v) was used as a granulating liquid. All formulations of pellets showed acceptable yield, aspect ratio and mechanical strength. The MCC pellets did not disintegrate and showed slow drug dissolution while the formulations with PEG 400 and/or polysorbate 80 disintegrated within 90 s and their drug dissolution was increased. The incorporation of CCS allowed the pellets to explode and disintegrate into two smaller pieces within 5 s after contact to an aqueous medium. The increased amount of CCS (from 2 to 10% w/w) insignificantly decreased disintegration time or increased drug dissolution. A slight difference in drug dissolution between freshly prepared pellets and pellets stored for 18 months may be due to the instability of drug in liquisolid environment. The results from this study suggest that the disintegrating or exploding MCC pellets could be prepared by incorporating PEG 400, polysorbate 80 and CCS, and promising for increasing dissolution of poorly water-soluble drugs.

Graphical abstractFast disintegrating microcrystalline cellulose pellets were developed in order to improve dissolution of a poorly water-soluble drug (i.e., indomethacin). Incorporation of polyethylene glycol 400, polysorbate 80 and croscarmellose sodium allowed the microcrystalline cellulose-based pellets to disintegrate or explode within a very short time, within seconds. Their drug dissolution was then improved greatly.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Rapidly disintegrating microcrystalline cellulose pellets were developed. ► Polyethylene glycol 400 and polysorbate 80 help to enhance pellet disintegration. ► Incorporated croscarmellose sodium allows the pellets to explode within seconds.