Figure 3: Porosity and disintegration as a function of compression force using loperamide tablets with 0% Kollidon CL-SF.
Kollidon CL-SF is a registered trademark of BASF SE. (ALL FIGURES ARE COURTESY OF BASF SE.)
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The hardness of loperamide HCl tablets was slightly reduced by increasing the tableting speed from 20 to 60 rpm, but disintegration
time remained constant (see Figure 4).
Figure 4: Hardness and disintegration as a function of tableting speed using loperamide tablets with 0% Kollidon CL-SF. Kollidon
CL-SF is a registered trademark of BASF SE. (ALL FIGURES ARE COURTESY OF BASF SE.)
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As expected, the disintegration times can be further shortened by the addition of Kollidon CL-SF (1% and 2%), which is accompanied
by a tendency toward higher hardness and lower friability. With these formulations, tableting pressures can be increased to
140 MPa without a negative impact on disintegration (see Figure 5).
Figure 5: Impact of additional Kollidon CL-SF on disintegration of loperamide tablets. Kollidon CL-SF is a registered trademark
of BASF SE. (ALL FIGURES ARE COURTESY OF BASF SE.)
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Surprisingly, even the low-dosed loperamide HCl tablets exhibited an acceptable standard deviation of content (4.98%) and
mass (0.53–0.81%), which may be caused by formation of interacting mixtures. There was 94.7% dissolution after 30 min for
the loperamide HCl tablets with 1% Kollidon CL-SF.
Table III: Properties of a caffeine tablet.
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Caffeine tablets gave similar results: 5.48% content uniformity, 0.98% mass variation, 100.6% dissolution after 10 min (see
Table III).
The addition of particular flavors such as chocolate improved the taste of the tablets significantly. Further tests with magnesium
stearate instead of sodium stearyl fumarate showed that significantly longer disintegration times were recorded caused by
the known lipophilizing effect of this compound (2).
Conclusion
Loperamide and caffeine orally dispersible tablets based on Ludiflash can be manufactured easily via a direct compression process. Optimal tableting pressure was found to be 60–10 MPa because this results in rapidly disintegrating,
mechanically stable tablets. Addition of small amounts of Kollidon CL-SF further shortened disintegration times and allowed
even higher tableting pressures (60–140 MPa). Tablet characteristics are only slightly influenced by compression speed.
S. Kruse is a laboratory expert, S. Gebert is a pharmaceutical engineer, K. Meyer-Böhm is a research and development (R&D) manager, A. Maschke, PhD, is a R&D manager, and K. Kolter*, PhD, is head of R&D for pharmaceutical excipients, BASF SE, G-EMP-MD-H201, Ludwigshafen, Germany, 67056, tel. + 49 621 6041664,
fax; 49 621 6097370, karl.kolter@basf.com
*To whom all correspondence should be addressed.
Submitted: Apr. 16, 2008; Accepted: Apr.24, 2008.
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References
1. R. Bohnacker et al., "Determination of the Disintegration Time of Mouth Melt Tablets with Texture Analyzer Method," Pharm. Ind. 67 (3), 327–35 (2005).
2. S. Rizk et al., "Influence of Lubricant Properties on Compression Behavior and Drug Dissolution Rate of Scleroglucan Hydrophilic
Matrix," Int. J. Pharm.
126 (1–2), 57–63 (1995).
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