Compaction behavior of isomalt after roll compaction

Isomalt is a polyol derived from sucrose. Advantages of this excipient are its sweet taste, which is supposed to allow taste masking, the low glycemic and insulinemic response (Petzoldt, 1982), and the ability to be compacted directly. With regard to infantile patients, also the lack of cariogenicity is important (Gehring, 1981). The marketed products differ mainly in the particle size distribution and the chemical composition.

Isomalt consists of varying amounts of 1-O-D-glucopyranosyl-D-mannitol dihydrate (GPM) and 6-O-D-glucopyranosyl- D-sorbitol (GPS). Since the water solubility of GPS is higher, the marketed products show deviating physicochemical behavior (Bolhuis, 2006). Ndindayino et al. (1999, 2002) investigated the performance of isomalt in direct compression. It was discovered, that isomalt exhibits plastic deformation and elastic recovery mostly in the die. One study determined that isomalt is also an option as diluent for orally disintegrating tablets (Chawla, 2011).

Moreover, isomalt was found to be beneficial as excipient for wet granulation with acetaminophen (Saska, 2010). Roll compaction/dry granulation is a frequently used operation in the pharmaceutical industry. As described in literature excipients can lose their ability to form strong tablets after roll compaction/dry granulation (Kleinebudde, 2004; Kochhar et al., 1995; Malkowska and Khan, 1983). Due to this work hardening called phenomenon, it is favourable to know how materials behave on recompression. As galenIQ 801 is a new brand of isomalt this study is planned out to investigate the preservation of its compactibility after roll compaction.

Abstract

Aim: Isomalt is an emerging excipient suitable for direct compression. In this study the suitability of the new isomalt grade galenIQ 801 for dry granulation and following tableting is evaluated.

Methods: Isomalt as well as a blend of equal parts with dibasic calcium phosphate (DCP) is roll compacted and tableted. Particle size distribution and flowability are assessed to characterize the raw material and granules. Tensile strength of tablets is related to the specific compaction force during roll compaction and to the tableting force. Furthermore, the friability and disintegration time are measured to see if the results correlate to the tensile strength and the calculated porosity of the tablets.
Results: In all cases, the tensile strength increases with raising tableting forces. However, the specific compaction force has a different influence. For isomalt the tensile strength is highest for tablets made from granules prepared at 2 kN/cm and 6 kN/cm and decreases at higher values, i.e. 10 kN/cm and 14 kN/cm. The tensile strength of the blend tablets is almost one third lower compared to the strongest tablets of pure isomalt (1.47 MPa versus 0.87 MPa for a specific compaction force of 6 kN/cm and a tableting force of 15 kN). Every tablet batch produced with the blend fails the friability test. Tablet batches of pure isomalt showing high tensile strengths pass the friability test. Disintegration time is longest when the tensile strength is at its maximum and decreases with higher porosity and lower tensile strengths.
Conclusion: Isomalt proves to be suitable for tableting after roll compaction. Even though the capacity as a binder might not be as high as of other excipients, it is a further alternative for the formulation scientist.
Download the publication here: Compaction behavior of isomalt after roll compaction

Julian Quodbach, Johanna Mosig, Peter Kleinebudde, Compaction behavior of galenIQ 801 after roller compaction, (doi:10.3390/ecps2012-00812)

Keywords: isomalt, roll compaction, work hardening, recompression, compactibility, galenIQ, Di-Cafos