Orally Disintegrating Tablets Using Starch and Fructose - Pharmaceutical Technology

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Orally Disintegrating Tablets Using Starch and Fructose
The authors demonstrated that ODTs can be obtained by direct compression of a mixture of starch, fructose, and SMCC.

Pharmaceutical Technology
pp. 92-99

Results and discussion

Figure 1: Effect of the type of the binder over disintegration time. MCC is microcrystalline cellulose and SMCC is silicified microcrystalline cellulose. SMCC1 is SMCC with an average particle size of 60 μm and a bulk density of 0.25–0.37 g/cm3. F1: 10% MCC; F2: 15% MCC; F3: 20% MCC; F4: 10% SMCC1; F5: 15% SMCC1; and F6: 20% SMCC1. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
Effect of the binder. More rapid disintegration times where obtained for 20% w/w of SMCC1 compared to when nonsilicified MCC was used at a similar tablet hardness (see Figure 1). In both cases, increasing the binder concentration decreased the disintegration times. Additionally, a higher porosity was observed when tablets exhibited low hardness (data not shown). A prior investigation of SMCC and MCC in comparable grades established very similar chemical and physical properties (15). However, improved mechanical properties make SMCC a superior tablet binder than MCC when used at similar concentrations (16, 17). The authors found that an increased tablet binder concentration decreased the disintegration times of SMCC1 tablets (see Figure 1). The SMCC enhanced compaction properties because of the presence of silicon dioxide, which is located mostly on the surface and occasionally embedded in MCC particles (18, 19). It is believed that this silicified form of MCC has brittle fracture properties, which enhance compaction when compared to native MCC (16). Moreover, Sherwood and Becker reported that MCC exhibited more sensitivity to the effect of lubricant than SMCC (20). The MCC tablets exhibited poor water penetration and slower disintegration times (see Figure 1). The MCC displays a high sensitivity to the effect of magnesium stearate inclusion, as observed by the high friability values observed with the MCC containing tablets. Previous work has suggested that the lubricant covers the surface of the powder particles, decreasing the mechanical properties of the tablet after compaction (21).

Figure 2: Effect of hardness and binder concentration on disintegration time for SMCC1 Formulation (F)4–F6), SMCC2 (F7–F9), and SMCC3 (F10–F12). SMCC is silicified microcrystalline cellulose. SMCC1 is SMCC with an average particle size (APS) of 60 μm and a bulk density (BD) of 0.25–0.37 g/cm3. SMCC2has an APS of 110 μm and BD of 0.25–0.37g/cm3, and SMCC3 has an APS of 110 μm and BD of 0.35–0.50g/cm3.
For all SMCC grades, increased tablet binder concentration decreased disintegration time (see Figure 2). Furthermore, increased amounts of SMCC1, SMCC2, and SMCC3 increased the porosity of the tablet batches (see Table II). Tablets that showed the highest porosity (14.88–17.09%) exhibited disintegration times of less than one minute (F6, F9, and F12). Most of the tablets in the high (5.6–6.8 kP) and medium (4.6 kP–5.5 kP) ranges of tablet hardness displayed acceptable friability values. With the exception of F9, at low tablet hardness (3.5–4.5 kP), increasing the concentration of binder decreased the tablet friability. The high friability values observed in F5, F7, F10, F11, and F12 are a consequence of tablets capping during the friability measurement, which resulted in a dramatic weight loss over the standard 5-min test period. This problem was seen when low concentration of SMCC was used (10% w/w and 15% w/w for all grades). It was also correlated with an increase in compression force, since it was observed only at high tablet hardness.

Table II: Porosity (%) and friability (%) values for formulations (F) containing SMCC1, SMCC2, and SMCC3 exhibiting low, medium, and high tablet hardness.
The differences observed among SMCC grades can be attributed to their physical properties. SMCC1 is a binder that was developed to be used in wet-granulation processes, while SMCC2 was developed for direct compression. Even though SMCC1 has good compaction properties, its small particle-size distribution has been reported to limit its flow characteristics (20). Furthermore, increased tablet hardness dramatically increased the disintegration times (see Figure 2), which ultimately limits usefulness of SMCC1 as a tablet binder in the formulation of ODTs. Mužíková and Nováková reported that SMCC2 showed better mechanical characteristics than its high density analogous, SMCC3 (21). This conclusion was supported by our results, where the best disintegration characteristics, friability, and porosity, were obtained for the SMCC2 grade, specifically at the high concentration (20% w/w) and lowest tablet hardness (see Figure 2 and Table II).


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