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.
Materials and methods
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.