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Development of Orally Disintegrating Tablets Based on a New Excipient
The authors examine the effectiveness of an excipient comprised of mannitol, polyvinyl acetate, and crospovidone using model actives loperamide hydrogen chloride and caffeine.
There is a strong trend in the pharmaceutical industry toward developing orally disintegrating tablets because they have various
benefits for the patient compared with regular tablets. These benefits include quick onset of action, ease of swallowing,
and the ability to take the tablets without water (1). To achieve these benefits, highly functional excipients are required.
Figure 1: Property triangle of fast dispersible excipients. (ALL FIGURES ARE COURTESY OF BASF SE.)
Rapid dissolution, smooth mouth feeling, and excellent compressibility are three properties of fast dispersible excipients
that are extremely important (see Figure 1). No single materials meet all these requirements, so Ludiflash (BASF SE, Ludwigshafen,
Germany) was developed. This formulated mixture of mannitol, polyvinyl acetate, and crospovidone is a highly functional material
that can be compressed directly and does not need complex and time-consuming processes such as mixer granulation, fluidized
bed granulation, roller compaction, or freeze drying.
Aim of the study
The goal of this study was to investigate how orally disintegrating tablets containing the model actives loperamide hydrogen
chloride (HCL) and caffeine can be developed. The effect of additional disintegrants and the impact of compression speed and
tableting force were studied applying a direct compression process.
Methods
Table I: Tablet composition.
Materials. The following materials were used in the study: a fast dispersible excipient (Ludiflash, BASF SE) based on mannitol, polyvinyl
acetate, and crospovidone; loperamide HCl (Selectchemie, Zurich, Switzerland); caffeine fine powder (BASF SE); sodium stearyl
fumarate (Pruv, J. Rettenmaier & Söhne GmbH + Co. KG, Rosenberg, Germany); and crospovidone (Kollidon CL-SF, BASF SE).
Table II: Compression and tablet data from a compression force study at 40 rpm .
Experimental methods. Various formulations of the active ingredients and excipients were compressed into tablets (see Table I). All ingredients
were blended in a Turbula blender (Bachofen, Uster, Switzerland) for 10 min and tableted on a rotary press (Korsch PH 106,
Korsch AG, Berlin, Germany) into flat tablets of 8 mm (loperamide HCl), respectively, 10 mm diameter (caffeine) with a bevelled
edge. The relative humidity (r. h.) inside the tablet press was adjusted < 20% r.h. The tableting speed was varied from 20
to 60 rpm and compression force from 1 to 16 kN.
Results
Figure 2: Hardness, friability, and disintegration as a function of compressed force using loperamide tablets with 0% Kollidon
CLSF. Kollidon CL-SF is a registered trademark of BASF SE. (ALL FIGURES ARE COURTESY OF BASF SE.)
The direct compression process was applicable to both model drugs with good results. The compression force study revealed
that for loperamide HCl tablets, 3–5 kN (60–110 MPa) should be applied because in this range disintegrating tablets of sufficient
hardness and low friability could be manufactured. A higher tableting pressure strongly reduces the porosity of the tablets
and results in longer disintegration times (see Table II, Figures 2 and 3).
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.
Articles by K. Kolter, PhD
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