Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors

Abstract

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder's particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder's capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required.

Keywords: alternate sourcing; compaction; compressibility; controlled release; density; direct compression; hypromellose; particle characteristics; tabletability.

Figure 1

SEM photomicrographs of HPMC K100M from different vendors: (a) Methocel CR, (b) Methocel DC, (c) Benecel CR, (d) Benecel DC, (e) Benecel XR, (f) Metolose 90SH, (g) Metolose 90SH SR, and (h) Bonucel. EDX analysis image of (i) Benecel DC.

Figure 2

FFC values and angle of wall friction (°) values of different HPMC grades tested using stainless steel coupons on the ring-shear tester. Note: vertical black numbers represents the values for both FFC and angle of wall friction. Error bars are omitted for clarity; standard deviations were in the range of 1.2–27.7%.

Figure 3

(a) Hardness (N) and (b) solid fraction data of the compacted polymer compacts from the various vendors after 24 h. Note: vertical black numbers represents the values for (a) hardness and (b) solid fraction. Error bars are omitted for clarity; standard deviations were in the range of 0.1–12.4% for hardness and 0.1–1.5% for the solid fraction.

Figure 4

(a) Tabletability profile and (b) compressibility profile (kN) of HPMC powders from different vendors under five compression forces (5, 7.5, 10, 12.5, and 15 kN). Note: vertical black numbers represents the values for (a) tabletability and (b) compressibility. Error bars are omitted for clarity; standard deviations were in the range of 0.3–12.5% for tabletability and 0.1–1.5% for compressibility.

Figure 5

Compaction properties of HPMC powders from different vendors. Relative tensile strength (RTS) (MPa) and porosity (%) relationship with compression stress (MPa) representing the respective tabletability and compressibility profiles at the same compression force (error bars are ±SD) for (a) Methocel DC, (b) Methocel CR, (c) Metlose 90SH SR, (d) Metlose 90SH, (e) BonuCel D, (f) Benecel DC, (g) Benecel XR, and (h) Benecel CR.

Figure 6

Compactibility of HPMC powders. Relative tensile strength (MPa) vs. tablet porosity (%) at five different compression stresses (error bars are ±SD) (for (a) Methocel DC, (b) Methocel CR, (c) Metlose 90SH SR, (d) Metlose 90SH, (e) BonuCel D, (f) Benecel DC, (g) Benecel XR, and (h) Benecel CR.

Figure 7

HPMC compaction curves of the polymers from the different vendors showing the relative density at various compaction pressures. (a) Methocel DC, (b) Methocel CR, (c) Metlose 90SH SR, (d) Metlose 90SH, (e) BonuCel D, (f) Benecel DC, (g) Benecel XR, and (h) Benecel CR.

Figure 7

HPMC compaction curves of the polymers from the different vendors showing the relative density at various compaction pressures. (a) Methocel DC, (b) Methocel CR, (c) Metlose 90SH SR, (d) Metlose 90SH, (e) BonuCel D, (f) Benecel DC, (g) Benecel XR, and (h) Benecel CR.

Figure 8

(a) In-die recovery (%) and (b) out-of-die axial expansion profile (%) of HPMC powders from different vendors under five compression forces. Note: vertical black numbers represents the values for (a) in-die recovery and (b) out-of-die axial expansion. Error bars are omitted for clarity; standard deviations were in the range of 4.2–7.6% for in-die recovery and 0.9–27.6% for out-of-die recovery.

Figure 8

(a) In-die recovery (%) and (b) out-of-die axial expansion profile (%) of HPMC powders from different vendors under five compression forces. Note: vertical black numbers represents the values for (a) in-die recovery and (b) out-of-die axial expansion. Error bars are omitted for clarity; standard deviations were in the range of 4.2–7.6% for in-die recovery and 0.9–27.6% for out-of-die recovery.

Figure 9

A plot of F2 vs. F1 showing the similarity between the measured properties.

Figure 10

A plot of the scores of all the material-associated properties for each compaction force on F2 vs. that on F1. Note, in the legend, the first number on the right of M indicates the material: 1—Benecel CR, 2—Benecel XR, 3—Benecel DC, 4—Methocel CR, 5—Methocel DC, 6—Metolose 90SH, 7—Metolose 90SH SR, and 8—BonuCel D. The second number on the right of M indicates the compaction force: 1—15 kN, 2—12.5 kN, 3—10 kN, 4—7.5 kN, and 5—5 kN.

Figure 11

A plot of scores on F1 showing how the material properties change with the compaction force.