The oral route of administration is considered to be the most preferred method of delivery and to date, tablets and capsules remain the most popular oral delivery systems.1,2 Not only do solid dosage forms meet the needs of many adult consumers by maintaining safety and accuracy, but their convenience also increases consumer compliance.3 And, although tablets and capsules may be a suitable answer for many, numerous consumers face difficulties when using solid dosage forms, such as the elderly, children or those with certain conditions who find swallowing difficult. For example, consider obstacles presented to a person with dysphagia, a condition that causes difficulty swallowing found in all age groups, but affects nearly 30 to 40 percent of the elderly population. When patients struggle with swallowing tablets or capsules, practitioners often see a lack of cooperation, which can result in non-compliance.4,5 Consumers, patients and practitioners have found oral disintegrating tablets (ODTs) provide the benefits of traditional tablets and capsules while meeting other commonly defined needs.
According to the U.S. regulation 21 CFR part 111, it is required that dietary supplements be made for oral dosing. As a non-invasive method of delivery for oral use only, ODTs are easily dosed and allow consumers to self-medicate safely without the need for additional fluid. The concept of ODTs has emerged with an objective to improve consumer compliance, particularly the products designed for pediatric and geriatric markets.6 These tablets are synonymous with the following: fast dissolving, fast melt, rapid melts, porous tablets, quick-dissolving tablets, etc. Regardless of the terminology used, these tablets are formulated to instantaneously begin disintegrating, and in turn release the intended active ingredients that dissolve and disperse in saliva.7 Depending on the physicochemical, pharmacokinetic and pharmacodynamic characteristics of the ingredients of the tablet, actives may be absorbed in the buccal, pharyngeal or gastric region of the gastrointestinal (GI) tract. Thus, ODTs offer several advantages over conventional tablets such as enhanced bioavailability, rapid onset of action and improved palatability.8,9
In recent years, ODTs have attracted attention, and the increased popularity has caused many governing bodies to define and set parameters for ODT products. All such products are classified by FDA as orally disintegrating tablets.10 Likewise, the European Pharmacopeia adopted the term “orodispersible tablets" for tablets that disperse or disintegrate in less than three minutes in the mouth before swallowing.11 According to the Center for Drug Evaluation and Research (CDER), ODTs are defined as “a solid dosage form containing medicinal substances which disintegrate rapidly, usually within a matter of seconds, when placed upon the tongue." In 2008, FDA issued a document titled, “Guidance for Industry: Orally Disintegrating Tablets," which provides further guidelines for industry. According to this guidance document, ODTs should have an in vitro disintegration time of approximately 30 seconds or less (per USP test method or equivalent) and the total tablet weight should not exceed more than 500 mg. This document also emphasizes an ODT should begin to disintegrate in the mouth within a matter of seconds.
Although some active ingredients can give tablets an undesirable flavor or odor, and cannot be avoided in formulation, the use of masking agents can help alleviate unpleasant flavors or aftertastes. As these tablets are designed to partially dissolve in close proximity to the taste buds, formulations should provide a pleasant flavor, good mouthfeel and minimal aftertaste, all of which contribute to consumer acceptance. Many other physicochemical properties of the ingredients, such as solubility, crystal morphology, particle size, hygroscopicity, compressibility and bulk density of the materials can also have a significant effect on the mechanical strength and disintegration of ODTs.12 Because of the distinct differences in dosage forms compared to conventional tablets, ODTs must maintain several critical attributes to achieve the intended purpose, with the most critical being disintegration. Typical formulation of an ODT contains a mixture of superdisintegrants, diluent, flavoring agents, binders and lubricants. Although each of these ingredients play an important role in the formulation, the type and amount of disintegrant impart the most impact on the overall success of the formulation, as these ingredients are directly related to the dissolving properties of the ODTs.13 An effective disintegrant should provide improved compressibility, compact-ability and compatibility without impacting the mechanical strength of the tablets. Carboxymethylcellulose, sodium starch glycolate and polyvinyl pyrolidone are commonly used in commercially available ODTs.
There are several ODT technologies that have been extensively reviewed in literature.14,15,16,17 Commercially available products include Zydis® (from Cardinal Health), OraSolv® and DuraSolv® (from Cima Labs), WOWTAB® (from Yamanouchi Pharma Technologies) and many more. Most of these technologies can be broadly categorized in groups based on the manufacturing method.
Freeze drying, molding, spray drying, direct compression, sublimation and mass extrusion are the most commonly used methods in the industry. Although all of these technologies have been successfully used to manufacture ODTs, direct compression is the most widely used method in the supplement industry because of its ease, simplicity and low manufacturing cost. Directly compressed ODT tablets can be manufactured using the same conventional equipment as traditional tablets without any prior treatment to the ingredients before compression. Although there are few supplement ingredients that can be compressed directly into tablets of acceptable characteristics and quality, excipients can be added to ODT formulas to overcome these obstacles. Methods such as freeze drying are relatively expensive, time consuming and cannot be used for thermolabile or moisture-sensitive substances. ODTs produced by this method are fragile, and tend to have poor stability at elevated temperatures and higher humidity.16 ODTs manufactured by molding are often poor in taste and relatively soft.18
ODT challenges remain, despite the progress of this technology. Hydrophobic actives and large dose sizes continue to challenge ODT production, especially in consideration to maintaining adequate disintegration properties. The future of ODTs requires improved formulation strategies in consideration of effective flavoring capabilities and improvement to friability. By increasing the physical integrity of the tablets, conventional multi-tablet packaging can be utilized.
Although there have been numerous advances in ODT technology, room for improvement remains in both formulation development and manufacturing.
Naeem Shaikh, Ph.D., leads the formulation team and drives the research that helps inspire and propel the product momentum at National Enzyme Co. (nationalenzyme.com). As an accomplished and published doctor, Shaikh leverages 28 years of renowned experience, with previous research ranging from micro-encapsulation to release methods for solid and liquid dosage forms.
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