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Orally Disintegrating Tablets
Orally disintegrating, or orodispersible, tablets (ODTs) are designed to dissolve in the presence of saliva within one minute. The primary advantage of ODTs is that no external source of liquid is needed for consumption. For patients with dysphagia or children too young to swallow tablets or capsules, ODTs provide a useful alternative. There are a variety of methods for preparing ODTs, including freeze drying, molding, compaction, granulation, spray drying, flash heat processing, sublimation to increase porosity, and direct compression. Disintegrating aids, binding agents, and sweeteners are added to the active drug moiety during production to improve the feel of the product in the mouth, making the dissolved drug smooth and creamy. Several companies have patented technologies for manufacturing ODTs, such as Zydis® (Catalent, Inc.) Flashtab® (Prographarm), Orasolv® (Cima), and Wowtab® (Yamanouchi Pharma Technologies).
Although the development of ODTs began in the 1970s, the first product to reach the US market, Claritin® Reditabs, was not approved by the FDA until December 1996. Since that time the number of ODT products has grown rapidly to include more than two dozen prescription and nonprescription drugs (Table).
While most currently available ODTs have been designed for adolescents and adults, some have been formulated specifically for younger patients, such as Children's Tylenol® Meltaways. These grape punch or bubble gum flavored tablets, designed for children 2–11 years of age, contain 80 mg acetaminophen and may be chewed or allowed to melt in the mouth.
An ODT formulation of prednisolone (Orapred ODT®) has proven to be very useful in pediatric patients with asthma or allergic conditions such as atopic dermatitis. Glucocorticoids are extremely bitter and the taste is difficult to mask, particularly in oral liquid products. The ODT product uses a triple layer polymer formulation to minimize the taste. Grape-flavored Orapred ODT® is currently available in 10 mg, 15 mg, and 30 mg strengths. In 2007, the manufacturer conducted a survey of 973 children; 89% reported a preference for the ODT product over prednisolone oral liquid. The primary disadvantage of this product is the cost; at $6 to $10 per tablet, it is considerably more expensive than other prednisolone preparations.
Ondansetron ODT (Zofran ODT® and generics) has been well accepted for the prevention or treatment of nausea and vomiting in the pediatric population. As with standard oral tablets, children 4–11 years of age may be given a 4 mg ODT three times daily. The dose for older children and adults is 8 mg taken three times daily. In 2008, Davis and colleagues enrolled 221 children (5–16 years of age) into a randomized, double-blind, placebo-controlled trial of ondansetron ODT after tonsillectomy. The incidence of emesis within the first 3 days after surgery was significantly lower in the ondansetron ODT group than in the placebo group (14.6% versus 32%, p = 0.004).
In one of the few prospective randomized pediatric studies to compare ODT products to standard formulations, Çorapçioglu and Sarper evaluated IV and ODT ondansetron products in 22 children (ages 3–17 years) with cancer. The children were randomized to receive either 5 mg/m2 IV ondansetron or a 4 or 8 mg ondansetron ODT 30 minutes before and 12 hours after chemotherapy. The percentage of patients experiencing a complete treatment response, defined as no nausea or vomiting, was no different between the groups (82% of the IV group and 85% of the ODT group, p= 0.981). Response rates remained similar when a subgroup of children receiving highly emetogenic regimens was analyzed (75% of the IV group and 80% of the ODT group, p = 0.931).
The ODT formulation is not without disadvantages. Most products are available in a single strength, often one that is too large for use in younger children. Because of their fragility, breaking, cutting, or splitting ODTs is not recommended. For some drugs, the rapid absorption from an ODT may result in a brief exposure to very high, potentially toxic, drug concentrations. New microencapsulation techniques provide a slower, more controlled release of drug from an ODT. Li and colleagues at the Shanghai Eighth People's Hospital have developed a scopolamine ODT that contains microparticles embedded with the drug. It dissolves within 45 seconds, but the drug itself is not completely absorbed into the bloodstream until 90 minutes after administration.
Another important concern is the potential for toxic ingestions of ODTs, particularly acetaminophen. Without the need to swallow, ODTs can be consumed in large numbers, even by very young children. In 2011, Ceschi and colleagues conducted a retrospective study of acetaminophen ingestions in children < 6 years of age reported to the Swiss Toxicological Information Center between June 2003 and August 2009. The authors compared 187 tablet ingestions and 16 cases involving The mean ingested dose was 59% greater in the ODT group (157.3 + 147.6 mg/kg compared to 98.7 + 77.7 mg/kg in the tablet group, p = 0.085). The authors suggest that the rapid dissolution of the ODT, as well as its sweet taste and candy-like feel in the mouth may encourage children to ingest more drug than what they would be able to swallow if tablets were involved.
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