Evaluation and Characteristics of a New Direct Compression Performance Excipient - Pharmaceutical Technology

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Evaluation and Characteristics of a New Direct Compression Performance Excipient
The authors investigated the tableting properties of PanExcea MHC300G, a high-performance excipient.


Pharmaceutical Technology
Volume 35, Issue 3


Figure 7: Tensile strength vs. compression force profile for tablets (10 mm diameter) prepared from 30%IBU/MHC300G/silica/stearic acid blend, and 30%IBU/Emcocel90/HPMC/CPVD/silica/stearic acid blend (IBU is ibuprofen, HPMC is hydroxypropyl methylcellulose, and CPVD is crospovidone).
A compaction profile was performed for various compression-force levels at constant turret-rotation speed (32 rpm) and tablet weight. Tablets were collected at each run to measure the average weight, thickness, breaking force (i.e., hardness) and disintegration times. The plots of tensile strength versus compression force (see Figure 6) show similar profiles and an increase in tensile strength with compression force for both MHC300G/Mg stearate and the blend of MCC/HPMC/CPVD/Mg stearate. MHC300G produces strong compacts (i.e., tablet radial-tensile strength of 1.2–4.5 MPa or tablet breaking forces of 95–260 N for 10-mm diameter compacts) in the compression-force range used in current tablet manufacturing (i.e., 5–15 kN) (see Figure 6). These values are lower than the ones corresponding to tablets prepared from MCC/HPMC/CPVD/Mg stearate blend. The results are not unexpected as it is well known that processing MCC via a wet-granulating technique results in some reduction of the compressibility of MCC, the mechanism of which is not well understood (23, 24). It has been suggested that the decrease in MCC compactibility after granulation is associated with the decrease in MCC primary particle porosity (23). The formulation containing 30% ibuprofen and PanExcea MHC300G, however, gives stronger compacts at compression forces up to 15 kN than the corresponding formulation containing MCC (see Table VI and Figure 7). Tablets prepared when using MHC300G are shown to retain the tensile strength (3.2 MPa for placebo and 3.0 MPa for 30% ibuprofen formulation at ~ 9 kN compression force) and the tensile strength of tablets prepared using the blend of MCC/HPMC/CPVD is reduced after mixing with ibuprofen (4.7 MPa for placebo and 2.5 MPa for 30% ibuprofen formulation at ~ 9kN compression force; see Figures 6 and 7). No significant tablet weight variation, capping or laminating tendencies were observed.


Figure 8: Variation in tablet weight with turret rotation speed for tablets (10 mm diameter) prepared from MHC300G/0.25%Mg stearate blend, and MCC/2%HPMC/9%CPVD/0.25%Mg stearate blend (MCC is microcrystalline cellulose, HPMC is hydroxypropyl methylcellulose, and CPVD is crospovidone).


Figure 9: Variation in tablet breaking force with turret rotation speed for tablets (10 mm diameter) prepared from MHC300G/0.25%Mg stearate blend, and MCC/2%HPMC/9%CPVD/0.25%Mg stearate blend (MCC is microcrystalline cellulose, HPMC is hydroxypropyl methylcellulose, and CPVD is crospovidone).
A strain-rate study was performed on both MHC300G/Mg stearate (0.25%) and a blend of MCC/HPMC (2%)/CPVD (9%)/Mg stearate (0.25%). The tablet properties and the tableting parameters were monitored when the turret-rotation speed was increased at constant compression force and tablet weight. Increasing the turret rotation speed from 13 rpm to 99 rpm led to very small change in tablet weight (~ 2.0 %) for MHC300G/Mg stearate, indicating that MHC300G shows a very good weight control throughout the full range of the tablet press (see Figure 8). The consistent weight control resulted in little compression-force variation. The tablet strength (i.e., breaking force) of the MHC300G compacts decreases with ~ 20% from 13 to 50 rpm showing a moderate strain-rate sensitivity at relatively low turret speeds, and levels off showing no strain-rate sensitivity for turret speeds ranging from 50 to 99 rpm (see Figure 9). Conversely, the blend of MCC/HPMC/CPVD/Mg stearate (0.25%) shows overall higher strain-rate sensitivity as evidenced by a 34% decrease in tablet weight (see Figure 8) and a 35% decrease in tablet strength (i.e., breaking force) when varying the turret speed from 13 to 99 rpm (see Figure 9). This is consistent with MCC being a ductile material that undergoes plastic deformation (25).


Figure 10: Variation in tablet weight with turret rotation speed for tablets (10 mm diameter) prepared from 30%IBU/MHC300G/silica/stearic acid blend, and 30%IBU/Emcocel90/HPMC/CPVD/silica/stearic acid blend (IBU is ibuprofen, HPMC is hydroxypropyl methylcellulose, and CPVD is crospovidone).
The strain-rate studies for formulations containing 30% IBU (see Table VI) indicated that both blends containing MHC300G and MCC show strain-rate sensitivity, with blends based on MHC300G having less strain-rate sensitivity. The decrease in average tablet weight when increasing turret-rotation speed from 13 rpm to 99 rpm (see Figure 10) was 3% for the IBU/MHC300G blend and 6% for IBU/MCC/HPMC/CPVD blend, respectively. This trend is paralleled by the change in tablet-breaking force (see Figure 11) as illustrated by an overall 40% loss of tablet strength for IBU/MCC/HPMC/CPVD/silica/stearic acid and ~ 25% loss of tablet strength for IBU/MHC300G/silica/stearic acid when increasing turret-rotation speed from 13 to 99 rpm. The tablets prepared in these tableting studies have excellent disintegration times, the tablet weight loss during the friability tests being negligible.


Figure 11: Variation in tablet breaking force with turret rotation speed for tablets (10 mm diameter) prepared from 30%IBU/MHC300G/silica/stearic acid blend, and 30%IBU/Emcocel90/HPMC/CPVD/silica/stearic acid blend (IBU is ibuprofen, HPMC is hydroxypropyl methylcellulose, and CPVD is crospovidone).
MHC300G dilution potential. The dilution potential can be defined as the amount of an active ingredient (API) that can satisfactorily be compressed into tablets with the excipient mixture.


Table VII: Bulk density, compressibility, and flowability index of IBU/MHC300G/SiO2 and IBU/MCC/HPMC/CPVD/ SiO2.
The dilution potential of MHC300G was studied using ibuprofen, which is an API that is difficult to tablet by DC. A 62.5% ibuprofen formulation, corresponding to the current commercial dosage, was prepared by using different grades of ibuprofen (20, 40 and 70 µm average particle size, respectively), MHC300G and 0.5% silica. The flowability of these blends was good as indicated by total flowability indices ranging from 76 to 85 and percent-compressibility indices ranging from 17 to 25. A similar blend prepared by using a mixture of MCC, HPMC (2%), CPVD (9%) and ibuprofen (20 µm) had poor flowability with a percent-compressibility index of 31, and a total flowability index of 62 (see Table VII). The API content uniformity for the blends containing PanExcea MHC300G was excellent, and the IBU recovery was in the range of 98–102% with %RSD < 2 (RSD is relative standard deviation).

Conclusion

PanExcea MHC300G was engineered as a performance excipient containing the three main components of a solid-dosage formulation: filler, binder, and a disintegrant. MHC300G is composed of homogeneous spherical particles in which the individual components cannot be distinguished from one another. Its physical properties and the consistency achieved by maintaining good control over the manufacturing process make this performance excipient ideal for use in drug-product manufacturing under the QbD principles. Placebo tableting studies by direct compression on a 10-station tableting machine showed very good weight control throughout the full range of the tablet press. The consistent weight control resulted in steady compression force when the turret speed was increased to 100 rpm. The tableting of MHC300G requires very little lubricant. Under the conditions used in this study, the resulted compacts were strong, with no capping tendency and excellent disintegration times. MHC300G has a very good dilution potential allowing the tableting of blends of up to 62.5% ibuprofen. Extended tabletability studies by direct compression of API/MHC300G blends with various percent content API will be reported in a follow-up paper.

Liliana A. Mīinea is a senior research chemist, Rajendra Mehta is a principal chemist, Madhu Kallam is an applications engineer, James A. Farina is a group leader of research and development (R&D), and Nandu Deorkar* is a director of R&D, all at Avantor Performance Materials (formerly Mallinckrodt Baker), 1904 J. T. Baker Way, Phillipsburg, NJ 08865, tel. 908.213.6720, fax 908.859.6932,
.

*To whom all correspondence should be addressed.

Submitted: Aug. 18, 2010. Accepted: Nov. 19, 2010.


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