An orally disintegrating tablet or orally dissolving tablet (ODT) is a drug dosage form available for a limited range of over-the-counter (OTC) and prescription medications. ODTs differ from traditional tablets in that they are designed to be dissolved on the tongue rather than swallowed whole. The ODT serves as an alternative dosage form for patients who experience dysphagia (difficulty in swallowing) or for where compliance is a known issue and therefore an easier dosage form to take ensures that medication is taken. Common among all age groups, dysphagia is observed in about 35% of the general population, as well as up to 60% of the elderly institutionalized population Sastry, S. et al., Pharm. Sci. & Tech. Today 3: 138-145, 2000.Groher ME, Bukatman MS. The prevalence of swallowing disorders in two teaching hospitals. Dysphagia. 1: 3-6, 1986. and 18-22% of all patients in long-term care facilities Layne KA, Losinski DS, Zenner PM, Ament JA. Using the Fleming index of dysphagia to establish prevalence. Dysphagia. 4: 39-42, 1989. ODTs may have a faster onset of effect than tablets or capsules, and have the convenience of a tablet that can be taken without water. During the last decade, ODTs have become available in a variety of therapeutic markets, both OTC and by prescription.
History Tablets designed to dissolve on the buccal (cheek) mucous membrane were a precursor to the ODT. This dosage form was intended for drugs that yield low bioavailability through the digestive tract but are inconvenient to administer parenterally, such as steroids and narcotic analgesics. Absorption through the cheek allows the drug to bypass the digestive tract for rapid systemic distribution. Not all ODTs have buccal absorption and many have similar absorption and bioavailability to standard oral dosage forms with the primary route remaining GI absorption. However, a fast disintegration time and a small tablet weight can enhance absorption in the buccal area. The first ODTs disintegrated through effervescence rather than dissolution, and were designed to make taking vitamins more pleasant for children. This method was adapted to pharmaceutical use with the invention of microparticles containing a drug, which would be released upon effervescence of the tablet and swallowed by the patient. Dissolution became more effective than effervescence through improved manufacturing processes and ingredients (such as the addition of mannitol to increase binding and decrease dissolution time). Catalent Pharma Solutions (formerly Scherer DDS) in the U.K., Cima Labs and Fuisz Technologies (whose founder Richard Fuisz went on to pioneer orally soluble films, a separate but related dosage form) in the U.S. and Takeda Pharmaceutical Company in Japan led the development of ODTs.
The first ODT form of a drug to get approval from the U.S. Food and Drug Administration (FDA) was a Zydis ODT formation of Claritin (loratadine) in December 1996.FDA Drug Details for Claritin RediTabs It was followed by a Zydis ODT formulation of Klonopin (clonazepam) in December 1997,FDA Drug Details for Klonopin Wafer and a Zydis ODT formulation of Maxalt (rizatriptan) in June 1998.FDA Drug Details for Maxalt-MLT The regulatory condition for meeting the definition of an orally disintegrating tablet is USP method 701 for Disintegration. FDA guidance issued in Dec 2008 is that ODT drugs should disintegrate in less than 30 seconds.FDA Guidance for Industry Orally Disintegrating Tablets This practice is under review by the FDA as the fast disintegration time of ODTs makes the disintegration test too rigorous for some of the ODT formulations that are commercially available.
Manufacturing/packaging The processes used to manufacture orally disintegrating tablets include loose compression tabletting, a process which is not very different than the manufacturing method used for traditional tablets and lyophilization processes. In loose compression, ODTs are compressed at much lower forces (4 – 20 kN) than traditional tablets. However, since ODTs are compressed at very low forces due to the need for them to be soft enough to disintegrate rapidly in the mouth, issues of material sticking to the die walls can be challenging. Typically, as in most tablet blends, lubricants such as magnesium stearate are added to the blend to reduce the amount of material that may stick to the die wall. Differences may be the use of disintegrating aids, such as crospovidone, and binding agents that aid in mouth feel, such as microcrystalline cellulose. Primarily, ODTs contain some form of sugar such as mannitol, which typically serves as the major diluent of the ODTs, and is also the primary contributor to the smooth and creamy mouth feel of most ODTs. Lyophilized ODT formulations may use proprietary technologies but can produce a tablet that has a faster disintegration rate, for example the Zydis ODT typically dissolves in the mouth in less than 5 seconds without water and Lyophilized Freeze drying tablets - ODT typically dissolves in the mouth in few seconds depending on the molecules and strength.
ODTs are available in HPDE bottles (Parcopa) or individually sealed in blister packs to protect the tablets from damage, moisture, and oxidation. Because ODTs are soft in nature, the ability to successfully package an ODT in a bottle is difficult. However, CIMA Labs markets their Durasolv ODT as being able to be placed into bottle for commercial sale, while CIMA's Orasolv is marketed for blisters only. Zydis ODT tablets manufactured by Catalent Pharma Solutions and Lyophilized Freeze drying tablets manufactured by Galien-LPS are delivered in a blister pack. The differences between the two CIMA products are proprietary, however, the primary difference is expected to be the use of microcrystalline cellulose (MCC), such as Avicel PH101, in the Durasolv product. MCC serves multiple purposes in an ODT but in the case of CIMA's products, it acts as a binder, increasing the internal strength of the tablet and making it more robust for packaging in bottles.
ODTs currently or previously available
Brand nameManufactured by/forGeneric availableActive ingredientCategoryIndicationIntended age Abilify DiscmeltAbilify Prescribing Information Otsuka America/Bristol-Myers Squibb yes aripiprazole Atypical antipsychotics Schizophrenia 13 years+Bipolar disorder10 years+Adjunct therapy for major depressive disorderadults Adzenys XR-ODT Neos Therapeuticsno amphetamine Amphetamines, Stimulants Attention deficit hyperactivity disorder 6 years+ Alavert Quick Dissolving Tablets Wyethyes loratadine Antihistamines Allergy 6 years+ Allegra ODT Sanofi Aventisyes fexofenadine Antihistamines Allergic rhinitis, UrticariaAllegra Prescribing Information 6–11 years Aricept ODT Eisai Co.yes donepezil Acetylcholinesterase inhibitors Alzheimer's disease adults Benadryl FastMelt Pfizeryes diphenhydramine Antihistamines Allergy 6 years+ Calpol Fast Melts McNeil Healthcare UKyes paracetamol Analgesics Pain 6 years+ Cipralex MELTZ Lundbeckyes escitalopram SSRIs, Antidepressant Major depressive disorder, Generalized anxiety disorder, Obsessive–compulsive disorder adults Clarinex RediTabs Schering-Ploughyes desloratadine Antihistamines Allergy 6 years+ Claritin RediTabs Bayeryes loratadine Antihistamines Allergy 6 years+ DDAVP Melt Ferring Pharmaceuticals desmopressin Antidiuretic Bedwetting, Central diabetes insipidus 5 years+ Edluar Meda AByes zolpidem Nonbenzodiazepine Hypnotics Short-term treatment of insomniaEdluar Prescribing Information adultsEtizest MDConsern etizolam Benzodiazepine analog/thienotriazolodiazepine Short-term treatment of anxiety and insomnia FazaClo AzurPharmayes clozapine Antipsychotics Treatment-resistant schizophreniaFazaClo Prescribing Information adults Fluimucil Alpex Pharma SA / Zambon Group N-acetylcysteine Mucolytic Cold and Cough 16 years+ Jr. Tylenol Meltaways McNeil Consumer Healthcareyes acetaminophen Analgesics, Antipyretics Pain, Fever 6 years+KemstroUCB Inc.nobaclofenMuscle relaxant, Antispastic Klonopin Wafers Rocheyes clonazepam Benzodiazepines, Anticonvulsant, Anxiolytics Seizure disorders infants+Panic disorderadults Lamictal ODT Aptalis / GlaxoSmithKlineyes lamotrigine Anticonvulsant, Mood stabilizer Seizure disorders 2 years+Bipolar I disorderadults Maxalt-MLT Merck & Co.yes rizatriptan Triptans, Serotonin agonists MigraineMaxalt Prescribing Information adults meloxicam orodispersible tablets Alpex Pharma Ltd (UK); Fontus Health Ltd (UK) meloxicam NSAIDs Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis 16 years+ Niravam Schwarz Pharmayes alprazolam Benzodiazepines, Anxiolytics Anxiety disorder, Panic disorder adults Nocdurna Ferring Pharmaceuticals desmopressin Antidiuretic Nocturia adults NuLev Alaven Pharmaceutical hyoscyamine anticholinergic / antispasmodic Peptic ulcer, Symptoms of various gastrointestinal and urinary disorders 2 years+ Nurofen Meltlets Reckitt Benckiser ibuprofen NSAIDs Pain, Fever, Inflammation 12 years+ Orapred ODT Sciele Pharmayes prednisolone Corticosteroids Asthma, Severe allergy, Hemolytic anaemia, Stevens–Johnson syndrome, Certain types of tuberculosis; acute treatment of arthritis, Bursitis, COPD, Leukemia, Lupus, Multiple sclerosis, Ulcerative colitisOrapred Prescribing Information adults and children weighing over 44 lbs/20.1 kg Parcopa Schwarz Pharmayes carbidopa/levodopa DDC inhibitors [carbidopa], Dopamine precursor [levodopa] Parkinson's diseaseParcopa Prescribing Information adultsPepcid RPDScherer DDS / MerckyesfamotidineHistamine H2-receptor antagonistsduodenal ulcer, gastric ulcer, gastroesophageal reflux disease, pathological hypersecretory conditionsadults Prevacid SoluTab Takeda Pharmaceuticalsyes lansoprazole Proton pump inhibitors Gastro-oesophageal reflux disease (GERD), Ulcers 1 year+Propulsid Quicksolv (withdrawn)Janssen PharmanocisaprideGastroprokinetic agentReglan ODTMeda Pharms, Schwarz PharmaFDA Drug Approval for Reglan ODTyesmetoclopramideAntiemetics, Dopamine receptor antagonistsshort-term therapy for GERD, acute diabetic gastric stasisadults Remeron SolTab Merck & Co.yes mirtazapine Antidepressants Major depressive disorder adults Risperdal M-Tab Janssen Pharmayes risperidone Atypical antipsychotics Schizophrenia 13 years+Bipolar disorder10 years+Irritability associated with autistic disorder5 years+Rybix ODTVictory PharmayestramadolOpioid, SNRI Pain16 years+ Saphris Merck & Co.no asenapine Atypical antipsychotics Schizophrenia, Bipolar disorder adultsStaxynBayer HealthcareyesvardenafilPhosphodiesterase 5 (PDE5) inhibitorErectile dysfunctionadult males Striant Buccal Columbia Laboratoriesno testosterone Androgen, Steroid hormone Hypogonadism (Low testosterone)adult males Suboxone tablets (also available as dissolvable film) Reckitt Benckiser no Buprenorphine/Naloxone semi-synthetic opioid partial opioid agonist & inverse opioid antagonist