Why Choose Orally Dissolving Tablets (ODTs)?

Orally dissolving tablets (ODTs) have revolutionized the pharmaceutical industry and patient care by enhancing drug life-cycle management and offering convenient dosing for patients who have difficulty swallowing, such as children, the elderly, and psychiatric patients. Since their market debut in the 1980s, demand for ODTs has steadily increased, fueling expansion of product pipelines. Three main drivers propel ODT development: patient needs, medication effectiveness, and manufacturing/marketing considerations.

Meeting Specific Patient Requirements

ODTs cater to patients who struggle to swallow traditional pills. These include:

• Pediatric, geriatric, and psychiatric patients who have difficulty swallowing or chewing solid dosages

• Patients afraid of choking on tablets or capsules

• Elderly patients who may forget doses of antidepressants

• Children who prefer ODT antihistamines over syrups

• Patients too nauseous from medical treatments to swallow medication

• Patients with ongoing nausea or limited water access

Boosting Medication Performance

ODTs offer higher bioavailability and faster onset compared to conventional preparations. Dispersion in saliva enables pregastric absorption for compounds that dissolve quickly, providing various absorption pathways like the oral cavity, pharynx, and stomach. This pregastric uptake reduces first-pass metabolism—a major plus for drugs extensively metabolized in the liver and gut. For such compounds, ODTs may improve safety by avoiding toxic metabolites. They also suit drugs largely absorbed in the oral cavity and gut, which bypass first-pass effects.

Expanding Marketing and Manufacturing Horizons

Innovation is critical for pharmaceutical companies to stay competitive once blockbuster patents expire. Transitioning drugs into more effective dosage forms extends patent protection and market exclusivity while also better meeting patient needs, boosting revenue. For example, Eisai Inc. responded to a generic challenge by launching Aricept ODT, a donepezil for Alzheimer's disease, line extension in Japan in 2004 and later, in the US in 2005. ODTs also let companies serve under-treated groups, improving brand and corporate images.

The Thriving ODT Market

The ODT market is not just prospering—it plays an indispensable role across therapy areas. In 2004, three categories dominated 92% of the global ODT market: Central Nervous System disorders (50% market share), Gastrointestinal diseases (29%), and Oncology (13%). This underscores ODTs' importance in managing conditions like GERD, pain, schizophrenia, Parkinson's, migraine, nausea, and sleep disorders.

From a financial view, the 2004 ODT market value neared $2.4 billion in ex-factory sales to wholesalers, reflecting ODTs' impact on pharma. Robust growth persisted, with 2006 forecasts predicting the market would top $3 billion including branded and generic ODTs. Experts predicted around 20% annual growth, alongside notable generic penetration claiming increased market share.

For context, the 2006 oral drug delivery market was worth approximately $35 billion, projected to reach $52 billion by 2010. ODTs, taste-masked preparations, and microemulsions accounted for 22% of this market, a remarkable figure given expectations for a 17% compound annual growth rate through 2010. This dynamic segment remains ripe for constant innovation in oral dosage forms.

The ODT market's strength is further evidenced by particular products' blockbuster sales. In 2013 alone, Zomig and Zomig-ZMT tablets generated $176 million, while Orapred ODT yielded approximately $33 million in 2014 U.S. revenues.

Consumer preferences also demonstrate ODTs' success and acceptance. Over half of surveyed patients preferred ODTs over conventional preparations. Even larger percentages said they would request ODTs from doctors (70%) or likely purchase ODTs (70%), with over 80% favoring ODTs over traditional tablets or liquids. For instance, in an infographic by Catalent, a innovative CDMO , on Zydis technology, patients prefer ODTs much more than traditional tablets.

src: Zydis technology inforgraphic - Catalent

Weighing ODT Advantages Against Limitations

As an innovation combining benefits of both standard tablets and liquids, ODTs offer several advantages along with certain limitations affecting their application.

ODT Benefits

Key benefits make ODTs a top choice for many patients and providers:

• No water needed: Can be taken without water, convenient for portability

• Rapid breakdown: Dissolve or disintegrate in saliva within seconds

• Palatable taste: Engineered for taste appeal and compliance

• Minimal residue: Leave little residue after dosing

• Compact and portable: Easy to transport

• Cost-effective production: Amenable to direct compression

• Patient-centered: Ideal for children, elderly, disabled

• Precise dosing: Unlike liquids

• Quick absorption: Fast breakdown enables rapid onset

• Enhanced bioavailability: Some compounds show improved absorption

• Lower first-pass metabolism: Increases bioavailability and reduces side effects

• Safety: Reduced choking risk versus tablets

• Release options: Allow for controlled release

• High drug load: Can hold significant drug amounts

Disadvantages and Limitations

Despite the benefits above, ODTs also face certain limitations including:

• Dose ceilings: Large doses (e.g. some antibiotics) pose formulation challenges

• Tablet fragility: Rapid breakdown makes ODTs more friable and difficult to handle

• Taste issues: Masking bitter flavors requires sophisticated technologies

• Moisture sensitivity: ODTs are hygroscopic, demanding specialized packaging and storage

• Tablet size/shape: Balancing ease of use and dosing can prove difficult

• Drug compatibility: Candidates must have adequate stability, solubility and permeability for oral absorption

Special Considerations

• Protecting ODTs from humidity requires meticulous packaging

• Taste masking techniques are needed including polymers, cyclodextrins, and proprietary methods like MicroMask®

Navigating ODT Development Challenges

Creating effective, patient-friendly ODTs involves solving complex puzzles—each piece must align perfectly. Developers tackle hurdles like ensuring good taste, tablet strength, moisture protection, and ideal drug loading.

Masking Bitterness

A major obstacle is ODTs’ innate unpleasant taste, demanding medicaments be taste-masked for patient compliance.

Optimizing Tablet Strength

ODTs must balance strength and fast breakdown in saliva—a tricky tradeoff. This typically requires soft compression or molding. Excessive force risks fragile tablets requiring specialized packing, increasing costs. Few patented methods like Wowtab® and Durasolv® offer adequate strength without compromising disintegration rate.

Battling Moisture

Like sugar cubes, many ODTs are hygroscopic, challenging to keep stable under normal conditions. Special moisture-protection packaging is often necessary.

Managing Drug Dose

Another issue is the feasible drug amount per tablet. Dose caps for lyophilized ODTs limit higher-dose or highly soluble medications.

Handling Solubility Issues

High solubility introduces problems like eutectic freezing point depression and glassy solid collapse upon drying. Matrix-forming excipients like mannitol help induce crystallinity, hardening tablets while maintaining desired properties.

Determining Ideal Size

Tablet size significantly impacts end-user experience. While smaller tablets around 7-8 mm are easier to swallow, larger sizes improve handling. Finding the right balance is key.

Surmounting these hurdles involves tremendous innovation paired with deep understanding of patient needs, driving ODT development forward.

Conventional Technologies for ODTs

ODTs' rapid breakdown and absorption stem from the novel application of several conventional pharmaceutical platforms.

Freeze Drying

Freeze drying (lyophilization) is fundamental to ODT production, involving freezing then reducing pressure to sublimate ice crystals, elegantly enabling heat-sensitive compounds. The resultant high surface area and porosity promote rapid dissolution and absorption, allowing quicker onset and potentially enhanced efficacy.

Tablet Molding

Tablet molding also plays a key role. Using water-soluble components and solvents yields highly porous tablets after air-drying, ensuring rapid disintegration in saliva and immediate effects.

Sublimation

Sublimation helps overcome slow dissolution of highly soluble ingredients in compressed tablets. By adding volatile materials like ammonium bicarbonate then removing them, tablets become highly porous with seconds-fast disintegration.

Spray Drying

Spray drying produces fine, porous powders. Combining these with gelatins, mannitol, disintegrants, and pH modifiers like citric acid or sodium bicarbonate, the resultant ODTs can breakdown in around 20 seconds upon water exposure.

Mass Extrusion

Mass extrusion softens drug blends before molding them into tablets via extrusion, allowing taste masking of bitter actives via coatings.

Direct Compression

The simplest, most cost-effective manufacturing method is direct compression. However, disintegration/dissolution rates depend heavily on the disintegrants and soluble excipients used, requiring careful optimization.

ODT Platform Overview

Zydis

• Developer: --

• Approval: Loratadine (1996), Clonazepam (1997), Rizatriptan (1998) by FDA

• Features: Fast-dissolving, lyophilized, blister packs, self-preserving

• Use: Dissolves on tongue in 2-3 seconds

• Formulation: Gelatin matrix for hardness/strength, freeze-dried blend

Durasolv

• Developer: CIMA Labs

• Features: Conventional tableting equipment, good rigidity, suitable for low dose drugs

• Packaging: Blisters or bottles

• Formulation: Fillers, lubricants, low friability, <60 sec breakdown

Orasolv

• Developer: --

• Features: Effervescence in saliva, low compression

• Packaging: Not specified

• Products: Tempra FirsTabs, Remeron SolTab

Orodis

• Developer: --

• Features: Compressed tablets, 15-30 sec disintegration, high hardness

• Packaging: Push-through blisters

MeltEase

• Developer: Nutrition Formulators

• Features: 5 sec average dissolution for 400mg tablet

• Markets: Children, elderly

• Packaging: Not specified

QuickDis

• Developer: Lavipharm Labs

• Features: Fast-dissolving films, intraoral delivery, 5-10 sec breakdown

• Packaging: Pouches, blisters

Wowtab

• Developer: --

• Features: Traditional granulation/tableting with saccharide combinations

• Tablet Hardness: 0-2 kg (low moldability) to >2 kg (high)

• Formulation: Saccharides for moldability/hardness

FlashDose

• Developer: Fuisz Tech

• Features: Compressed granular excipients, conventional agents

• Formulation: Disintegrating and swelling components

Flashtab

• Developer: --

• Features: Shearform/Ceform platforms, bitter taste masking

• Products: Nurofen meltlet (Ibuprofen)

• Packaging: Not specified

OraQuick

• Developer: KV Pharma

• Features: MicroMask microspheres for taste masking, heat-sensitive drug friendly

• Formulation: Powder protection, microencapsulation, high strength

NanoCrystal

• Developer: Elan

• Features: Improves dissolution, suitable for ODTs

• Formulation: Particle size <1000 nm via milling, lyophilized wafers

Dispersible Tablet

• Developer: --

• Features: Sub-1 min disintegration

• Drugs: Dihydroergotoxine, cimetidine

• Formulation: Organic acids, disintegrating agents

Future Outlook

ODTs show immense promise for advancing drug delivery. We can expect continued pipeline growth encompassing generic, veterinary, and enhanced 'supergeneric' applications.

One major goal is developing quality control methods tailored specifically to evaluate ODTs' unique properties, ensuring batch consistency and performance benchmarks are met.Another prospect lies in leveraging ODTs to deliver peptide/protein therapies. Traditional oral delivery struggles with bioavailability for these compounds due to rapid GI degradation. ODT breakdown in saliva could enable exceptional bioavailability.Other areas of expected progress include controlled-release ODT platforms, which would benefit short half-life drugs, along with formulation improvements to accommodate larger doses and lipophilic compounds. Additionally, we may see delayed-release ODTs emerge with sophisticated controlled release and fixed-dose combinations, heralding a new generation of patient-centric medication delivery systems.

In summary, ODTs are poised for transformative advances in coming years, bringing unprecedented treatment efficacy and convenience across myriad therapeutic applications. The impacts on patients and healthcare overall promise to be profound.

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