The orally disintegrating tablet (ODT) is a solid dosage form that disintegrates and dissolves in the mouth without the need
of water within 60 seconds or less (1). According to the US Food and Drug Administration, ODT is "a solid dosage form containing
medicinal substances, which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue" (2). By
FDA guidance, ODTs should have an in vitro disintegration time of 30 seconds or less, based on the US Pharmacopeia disintegration test method.
ODTs are also called fast-disintegrating, orodisperse, mouth-dissolving, quick-dissolve, fast-melt, and rapid-disintegrating
tablets, and freeze-dried wafers (3–5). They are different from conventional sublingual tablets, lozenges, and buccal tablets,
which require more than one minute to dissolve in the mouth. In 2005, ODTs were the only quick-dissolving dosage form recognized
by FDA and listed in the Orange Book (6).
ODTs have attracted attention as an alternative to conventional oral dosage forms such as tablets and capsules due to their
advantages of convenient administration, increased patient compliance, and as a way to extend the product life cycle of a
drug. For example, recent market studies indicate that more than half of the patient population prefers ODTs to conventional
tablets or capsules. One very practical reason is that many patients such as children and the elderly have difficulty swallowing
tablets and capsules. There are other patients who simply prefer the convenience of a readily administered dosage form like
an ODT. In addition, there are business needs that drive ODT development as a means to expand product lines, improve life-cycle
management, and extend patent life. It is not a surprise, therefore, to see that the demand for ODT-adapted drugs is forecast
to increase 8.9% annually to nearly $2.6 billion in 2012 (7).
ODTs can be made by direct compression (DC), lyophilization, and molding technologies (4, 8, 9). Of these manufacturing processes,
DC is the most economical as it uses conventional equipment, commercially available excipients, and relatively simple process
steps. This study chose DC as the manufacturing process to produce ODTs.
The disintegration rate of ODTs is a critical success factor. For ODTs produced through the DC process, the disintegration
time depends on the disintegrants, matrix, tablet weight, and tablet hardness. In many cases, the disintegrant has a major
role in the disintegration process, and the disintegrant use level will impact tablet hardness and mouthfeel. The choice of
a suitable disintegrant and an optimal use level, therefore, are critical to ensure a high disintegration rate.
Table I: Commercial superdisintegrants.
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The objective of this study was to evaluate the functionality and performance of three types of commonly used commercial superdisintegrants,
crosslinked croscarmellose sodium (XL-CMC), crospovidone, and sodium starch glycolate (SSG), in the application of ODTs. For
each superdisintegrant, a wide range of disintegrant use levels (0.5–20%) was investigated in commonly used ODT model matrices
at different compaction forces (4–12kN). Tablet disintegration time, hardness, friability, and stability were compared. An
optimal use level was identified for each superdisintegrant. A further comparison between XL-CMC and crospovidone in mouthfeel
was conducted at their optimal use level. In addition, an analytical method was developed to monitor the ODT-softening process
in a small amount of water to mimic the oral cavity condition.
Materials and methods
Figure 1: The chemical structures of the three superdisintegrants: crosslinked croscarmellose sodium (XL-CMC), crospovidone,
and sodium starch glycolate (SSG) (ALL FIGURES ARE COURTESY OF THE AUTHORS)
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Materials.
Pearlitol 200 SD (Roquette, Paris), a direct-compressible mannitol, was used as a tablet matrix former. Magnesium stearate
(Mallinckrodt, St. Louis, MO) was used as a lubricant. The superdisintegrants evaluated in this study were obtained from commercial
suppliers and used as received (see Table I). The chemical structures of the three superdisintegrants are shown in Figure
1.
Table II: Placebo orally disintegrating tablet formulations.
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ODT preparation and evaluation.
Formulation design and tablet preparation. The detailed formulations that were used to evaluate the four commercial superdisintegrants (three types) in typical mannitol
ODT model matrixes are shown in Table II.
To prepare each formulation, Pearlitol 200 SD and the disintegrant were weighed and premixed in a V-blender for 15 min. Magnesium
stearate (MgSt) was added and mixed for an additional 2 min. The batch size for each formulation is 1 kg.
To prepare the tablets, each formulation was compressed individually on a tablet press (Stokes 512, Stokes-Merrill, Bristol,
PA) with four stations. Standard 7/16 in. concave punches and corresponding dies were used. Tablet weight was adjusted to
400 mg. A data-acquisition system (SMI Director, SMI Incorporated, Lebanon, NJ) was used to record compaction process. A series
of compaction forces, 4kN, 6kN, 8kN, 10kN, and 12kN were applied to each formulation to produce tablets with different levels
of hardness.
Figure 2: Tablet disintegration time overview.
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Characterization of ODTs. Disintegration times of the tablets were determined using a disintegration test system (Hanson QC-21, Hanson Research, Chatsworth,
CA). The test was conducted at 37 ± 0.5 °C in a medium of distilled water. Six tablets per sample were analyzed, and the mean
was reported (see Figure 2).
