MUPS Tableting-Comparison between Crospovidone and Microcrystalline Cellulose Core Pellets

Abstract

Multi-unit pellet system (MUPS) tablets were fabricated by compacting drug-loaded pellets of either crospovidone or microcrystalline cellulose core. These pellets were produced by extrusion-spheronization and coated with ethylcellulose (EC) for a sustained drug release function. Coat damage due to the MUPS tableting process could undermine the sustained release function of the EC-coated pellets. Deformability of the pellet core is a factor that can impact the extent of pellet coat damage. Thus, this study was designed to evaluate the relative performance of drug-loaded pellets prepared with either microcrystalline cellulose (MCC) or crospovidone (XPVP) as a spheronization aid and were comparatively evaluated for their ability to withstand EC pellet coat damage when compacted. These pellets were tableted at various compaction pressures and pellet volume fractions. The extent of pellet coat damage was assessed by the change in drug release after compaction. The findings from this study demonstrated that pellets spheronized with XPVP had slightly less favorable physical properties and experienced comparatively more pellet coat damage than the pellets with MCC. However, MUPS tablets of reasonable quality could successfully be produced from pellets with XPVP, albeit their performance did not match that of vastly mechanically stronger pellets with MCC at higher compaction pressure.

Keywords: MUPS tablet; compaction energy; crospovidone; ethylcellulose; microcrystalline cellulose; pellet coat damage; pellet core; spheronization aid.

Figure 1

SEM images of (a) MCC and (b) XPVP pellets that were (i) uncompacted or compacted at (ii) 10, (iii) 20, (iv) 30, and (v) 40 MPa. Pellets still embedded in the surface of the MUPS tablet compacted at (vi) 30 and (vii) 40 MPa are encircled by a red dashed line.

Figure 2

Tensile strength values (n = 5) of control tablets (∎) and MUPS tablets compacted at various compaction pressures containing MCC (∎) or XPVP pellets (∎). Error bars indicate the standard deviation and * denotes a significant (p < 0.05) difference.

Figure 3

Compaction energy data obtained from the Analis software for control tablets (∎) (n = 5) and MUPS tablets (n = 4) containing MCC (∎) or XPVP pellets (∎) compacted at various compaction pressures, comprising (a) plastic, (b) compression, (c) rearrangement, and (d) elastic energy. Error bars indicate the standard deviation and * denotes a significant (p < 0.05) difference.

Figure 4

Plots of compaction energies over the number of MCC () and XPVP () pellets contained in the MUPS tablet (n = 4). (a) Rearrangement energy, (b) plastic energy, (c) compression energy, and (d) ejection energy. Error bars represent the standard deviation. Trendlines (dotted) were fitted to discern trends. Control tablets (n = 5) acted as the baseline, and their compaction properties are indicated by a horizontal line (solid) with the bracketing as standard deviation lines (dashed).

Figure 5

Disintegration times of control tablets (∎) and MUPS tablets prepared with MCC (∎) and XPVP (∎) pellets at various (a) compaction pressures, where the error bars represent the standard deviation (n = 5) and (b) pellet volume fractions, where each symbol represents an individual sample, the solid horizontal line represents the disintegration time of the control tablets, and the bracketing represents the standard deviation lines (dashed).

Figure 6

(a) MET released over time and (b) MET release-rate values per time period for (i) MCC and (ii) XPVP pellets compacted at 10 (∎), 20 (∎), 30 (∎), and 40 MPa (∎). Uncompacted pellets (∎) acted as control. Error bars indicate the standard deviation, and significant differences were omitted for clarity (n = 4).

Figure 7

(a) K values of MCC (∎) and XPVP (∎) pellets tableted at various compaction pressures (n = 4). Error bars represent the standard deviation and * denotes a significant (p < 0.05) difference. (b) Plot of K values over tablet elastic energy where error bars were omitted for clarity (n = 4).

Figure 8

(a) MET released over time of (i) MCC and (ii) XPVP pellets compacted into MUPS tablets at 30 MPa with pellet volume fraction level I (), II (), III (), IV (), V (), VI (), and VII (). Error bars represent the standard deviation (n = 4). Plots of (b) K and (c) IDR values against pellet volume fractions for MCC () and XPVP () pellets. Each symbol represents an individual sample. Approximated trendlines and critical pellet volume fractions are shown for the respective pellets using solid and dashed lines, respectively.