Orally disintegrating tablets (ODTs) are solid dosage forms that rapidly dissolve in the mouth without the need for water, typically within seconds to a minute. They are designed to improve patient compliance, especially for those with difficulty swallowing, by providing a convenient and easy-to-administer alternative to traditional tablets.
In this article, we’ll explore what ODTs are, their benefits, formulation challenges, manufacturing techniques, and regulatory considerations.
How They Work
ODTs use excipients which facilitate rapid disintegration upon contact with saliva, allowing for faster absorption and, in some cases, faster onset of action. These excipients quickly absorb water and swell, thus disintegrating and breaking the tablet.
There is increased demand for these dosage forms due to the various benefits they offer, most notably convenience for pediatric, geriatric, and other individuals with dysphagia (difficulty swallowing). The mechanism of ODTs also has the benefit of bypassing first-pass liver metabolism, thereby increasing bioavailability.
Benefits of ODTs for Patients and Drug Developers
ODTs offer several advantages over traditional tablets and capsules, including:
- Improved Patient Compliance: Ideal for young children, elderly patients, and individuals with swallowing difficulties.
- Convenience: No need for water, making them perfect for travel or emergency situations.
- Faster Onset for Certain Drugs: Some ODTs may allow for faster drug absorption, directly increasing maximum plasma concentration of the drug (Cmax) and decreasing the time to achieving Cmax (Tmax).
- Enhanced Drug Bioavailability: In some cases, ODTs can improve drug absorption compared to standard oral tablets. This is because of bypassing the low pH environment of the stomach, the variety of enzymes found in the gastrointestinal (GI) tract, and because of bypassing the first-pass metabolism of the liver, wherein drugs are metabolized and deactivated in the liver prior to entering systemic circulation.
Considerations for ODT Formulation Development
Developing ODTs involves balancing factors which affect rapid disintegration, mechanical strength, taste masking, patient acceptability, and drug stability. Some key formulation considerations include:
- Excipients Selection: Superdisintegrants (e.g., crospovidone, croscarmellose sodium) help ODTs break down quickly. Flavoring agents and sweeteners improve taste. Some excipient vendors offer excipient systems which can speed up formulation development when used in combination with the active pharmaceutical ingredient (API) and reduce the time to market.
- Taste Masking: Excipients that have pleasing taste are preferred. For example, mannitol is a preferred filler for taste-masking since it has a sweet taste and creates a cooling sensation in the mouth. Many active pharmaceutical ingredients (APIs) have a bitter taste and require taste-masking technologies such as ion exchange resins, coating techniques, or complexation with cyclodextrins. Similar to chewable tablets, excipient particle sizes must be sufficiently reduced to prevent grittiness of the final tablet formulation and improve mouthfeel.
- Mechanical Strength vs. Fast Disintegration: ODTs must be robust enough for packaging and handling but still disintegrate rapidly in the mouth. This requires careful optimization of tablet hardness and friability.
- Packaging Selection: ODTs must be kept away from moisture. Since they tend to be more friable than conventional tablets, using cotton in packaging bottles can help minimize breakage. Some ODT formulations which are very fragile may require blister packs or moisture-resistant containers to maintain the product’s physical integrity.
Manufacturing Techniques for ODTs
There are several methods for manufacturing ODTs, each with its own advantages:
- Direct Compression: The most cost-effective and widely used method, involving the use of superdisintegrants and taste-masking agents.
- Lyophilization (Freeze-Drying): Produces highly porous tablets with rapid disintegration, but the process is expensive and requires specialized equipment.
- Molding: Creates highly porous tablets with good mouthfeel, but they may have lower mechanical strength. Not the preferred process since not many CDMOs have this capability at scale.
- Sublimation: Uses volatile substances to create a porous matrix for rapid disintegration.
The choice of manufacturing method depends on the drug’s properties, stability requirements, and cost considerations. Direct compression or use of granulation is most often the go-to method of manufacturing due to its low cost and long history of advancements in its technology.
Regulatory and Quality Considerations for ODTs
Regulatory agencies like the FDA and ICH have specific guidelines for ODTs, including:
- Disintegration Time: The FDA recommends that ODTs have in-vitro disintegration times of approximately 30 seconds or less.
- Dissolution Testing: Ensuring consistent drug release and bioavailability.
- Stability Requirements: ODTs must maintain potency, disintegration properties, and taste over their shelf life.
- Analytical Method Development: Specialized testing methods are needed to evaluate the mechanical strength, moisture sensitivity, and uniformity of ODT formulations.
Pharmaceutical companies must also consider tablet size when developing ODTs. Although this is also important for conventional tablets, the tablet size of an ODT can compromise the rapid disintegration time and patient acceptability. Formulation challenges may arise as higher drug loads can impact tablet integrity and mouthfeel.
Optimize your Formulation Development with Vici
Orally disintegrating tablets provide a valuable alternative to traditional solid dosage forms, offering convenience, improved compliance, and in some cases, faster drug absorption. However, their development requires careful attention to formulation, manufacturing, and regulatory compliance. As demand for patient-friendly medications continues to rise, ODT technology is expected to play an increasingly important role in the pharmaceutical industry.
For companies looking to develop ODT formulations, partnering with an experienced CDMO ensures optimized excipient selection, robust taste-masking strategies, and scalable manufacturing processes that meet regulatory requirements. Contact us today to learn more about how Vici can formulate, test, and manufacture ODTs for your drug development program.
