Understanding the Multidimensional Effects of Polymorphism, Particle Size and Processing for D-Mannitol Powders

Abstract

The relevance of the polymorphic form, particle size, and processing of mannitol for the mechanical properties of solid oral dosage forms was examined. Thus, particle and powder properties of spray granulated β D-mannitol, β D-mannitol, and δ D-mannitol were assessed in this study with regards to their manufacturability. D-mannitol is a commonly used excipient in pharmaceutical formulations, especially in oral solid dosage forms, and can be crystallized as three polymorphic forms, of which β is the thermodynamically most stable form and δ is a kinetically stabilized polymorph. A systematic analysis of the powders as starting materials and their respective roller compacted granules is presented to elucidate the multidimensional effects of powder and granules characteristics such as polymorphic form, particle size, and preprocessing on the resulting tablets' mechanical properties. In direct compression and after roller compaction, δ polymorph displayed superior tableting properties over β mannitol, but was outperformed by spray granulated β mannitol. This could be primarily correlated to the higher specific surface area, leading to higher bonding area and more interparticle bonds within the tablet. Hence, it was shown that surface characteristics and preprocessing can prevail over the impact of polymorphism on manufacturability for oral solid dosage forms.

Keywords: direct compression; mannitol; polymorphism; powder characterization; processability; roller compaction; surface area; tabletability.

Figure 1

Scanning electron microscopy images of (a) δ mannitol powder, (b) δ mannitol granules, (c) β mannitol powder, (d) β mannitol granules, (e) spray granulated Parteck M200, and (f) spray granulated Parteck M200 after roller compaction at 500× magnification. Regions with high surface roughness after roller compaction marked in yellow.

Figure 2

(a) Tabletability and (b) compactability plots of δ mannitol and β mannitol powder and granules. Arithmetic means of n = 10 ± S.D.

Figure 3

The percentage of elastic recovery for δ and β mannitol powder and their respective granules. Arithmetic means of n = 10 ± S.D.

Figure 4

Heckel Yield pressure of δ and β mannitol powder and their respective granules. Arithmetic means of n = 10 ± S.D.

Figure 5

Compactability of δ mannitol, β mannitol, and 180 µm sieved β mannitol powder and granules. Arithmetic means of n = 10 ± S.D.

Figure 6

The percentage of elastic recovery for δ mannitol, β mannitol, and 180 µm sieved β mannitol powder and granules. Arithmetic means of n = 10 ± S.D.

Figure 7

(a) Tabletability and (b) compactability plot of δ and β mannitol, β mannitol sieved through 180 µm sieve, and spray granulated β mannitol and their respective roller compacted granules. Arithmetic means of n = 10 ± S.D.

Figure 8

Heckel yield pressure of δ and β mannitol, β mannitol sieved through 180 µm sieve, and spray granulated β mannitol and their respective roller compacted granules. Arithmetic means of n = 10 ± S.D.

Figure 9

The percentage of elastic recovery for δ and β mannitol, β mannitol sieved through 180 µm sieve and spray granulated β mannitol and their respective roller compacted granules. Arithmetic means of n = 10 ± S.D.