An Alternative to the USP Disintegration Test for Orally Disintegrating Tablets

The authors propose an alternative to the USP disintegration test method. The method embraces physiological conditions of the oral cavity, as a screening tool for developing ODT products.
Aug 02, 2008
Volume 32, Issue 8

Orally disintegrating tablets (ODTs) are designed to dissolve or disintegrate rapidly upon contact with saliva to eliminate some common problems for oral solid-dosage forms such as difficulty in swallowing (dysphagia), the need for chewing a tablet, and the need for water intake (1). The Center for Drug Evaluation and Research's (CDER's) Data Standards Manual for Dosage Forms provides the original definition of an ODT as "a solid dosage form containing medicinal substances which disintegrates rapidly, usually within a matter of seconds, when placed upon the tongue (2)." Ideally, an ODT dissolves or disintegrates quickly in a few seconds it is placed on the tongue without the intake of water. ODTs can be used for incorporating additional clinical benefits such as enhancing oral absorption and bioavailability, improving patient compliance, and for business purposes such as extending patent life, product life cycle, and product differentiation (3).

Recently, increasing numbers of active pharmaceutical ingredients (APIs) have been formulated into orally disintegrating dosage forms. The current market consists of more than 145 launched products (both branded and generic) for 92 molecules (and combinations), which is an increase of 10 molecules and more than 15 brands from 2004, including prescription and over-the-counter (OTC) segments. ODT therapies for central nervous system disorders (depression, mood disorders, migraine headaches, Alzheimer's disease, insomnia, anxiety) still dominate the market, accounting for more than 40% of the market value. Gastrointestinal (GI) ODTs increased in share to 34% by value, oncology to 10%, and diabetes to 7%. In 2005–2006, brand companies learned that patients perceived a faster onset of action with an ODT, and caregivers welcomed the ease of administration of ODTs to patients who are reluctant to comply with medical orders or who became combatant when administered their medicine. These are likely the contributing factors to the high growth in the ODT market (4).

In 1998, the definition of an orally dissolving or disintegrating tablet appeared in a compendial publication for the first time. According to the recently issued Draft Guidance for Industry of Orally Disintegrating Tablets (1), FDA specifically recommends that, in addition to the original definition for an ODT, ODTs be considered solid oral preparations that disintegrate rapidly in the oral cavity, with an in vitro disintegration time of approximately 30 s or less according to the United States Phamacopeia (USP) disintegration method or alternative. Although tablet size and weight are not explicitly included in the definition, in view of patient safety and compliance, the agency recommends that the weight of the tablet not exceed 500 mg.

Presently, neither USP nor the European Pharmacopoeia has defined a specific disintegration test for ODTs. The results from the USP disintegration test ‹701› do not provide a strong correlation with in vivo disintegration times in the mouth because the test uses a disintegration medium of about 900 mL of water and a vigorously oscillating apparatus, which provide conditions far than those found in vivo (5). According to a test method reported in the 12th Annual FDA Science Forum (6), currently there is no USP in vitro method for evaluating disintegration time for ODTs, which represents in vivo disintegration time in the mouth. Therefore, FDA recommends using a modified form of the USP disintegration test ‹701›. A quick and simple modified test was designed to help regulatory review scientists in evaluating the ODTs. Using a disposable syringe, 1 mL of water is delivered directly onto a tablet placed on a flat surface. Completeness of disintegration of the tablet is checked by the manual palpation of the tablet at the end of 30 s, which is set by FDA as the disintegration specification for ODTs. The proposed test method requires minimum equipment so that it allows review scientists to evaluate, in an office setting, the disintegration of ODTs submitted for approval. It also can serve as a quick screening tool for review scientists to decide whether a dosage form is appropriately labeled as an ODT. Incomplete disintegration may require further laboratory testing on the product or justification by the firm to label the product as an ODT.

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