Orally disintegrating tablet


An orally disintegrating tablet or orally dissolving tablet is a drug dosage form available for a limited range of over-the-counter 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 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 and 18-22% of all patients in long-term care facilities
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 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. Catalent Pharma Solutions in the U.K., Cima Labs and Fuisz Technologies 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 was a Zydis ODT formation of Claritin in December 1996. It was followed by a Zydis ODT formulation of Klonopin in December 1997, and a Zydis ODT formulation of Maxalt in June 1998. 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. 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 than traditional tablets. However, since ODTs are compressed at very low forces due to the need to 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 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, 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 DiscmeltOtsuka America/Bristol-Myers SquibbyesaripiprazoleAtypical antipsychoticsSchizophrenia13 years+
Abilify DiscmeltOtsuka America/Bristol-Myers SquibbyesaripiprazoleAtypical antipsychoticsBipolar disorder10 years+
Abilify DiscmeltOtsuka America/Bristol-Myers SquibbyesaripiprazoleAtypical antipsychoticsAdjunct therapy for major depressive disorderadults
AbstralSentynl TherapeuticsfentanylOpioidBreakthrough pain in persons with canceradults
Adzenys XR-ODTNeos TherapeuticsnoamphetamineAmphetamines, StimulantsAttention deficit hyperactivity disorder6 years+
Alavert Quick Dissolving TabletsWyethyesloratadineAntihistaminesAllergy6 years+
Allegra ODTSanofi AventisyesfexofenadineAntihistaminesAllergic rhinitis, Urticaria6–11 years
Aricept ODTEisai Co.yesdonepezilAcetylcholinesterase inhibitorsAlzheimer's diseaseadults
Benadryl FastMeltPfizeryesdiphenhydramineAntihistaminesAllergy6 years+
Calpol Fast MeltsMcNeil Healthcare UKyesparacetamolAnalgesicsPain6 years+
Cipralex MELTZLundbeckyesescitalopramSSRIs, AntidepressantMajor depressive disorder, Generalized anxiety disorder, Obsessive–compulsive disorderadults
Clarinex RediTabsSchering-PloughyesdesloratadineAntihistaminesAllergy6 years+
Claritin RediTabsBayeryesloratadineAntihistaminesAllergy6 years+
DDAVP MeltFerring PharmaceuticalsdesmopressinAntidiureticBedwetting, Central diabetes insipidus5 years+
EdluarMeda AByeszolpidemNonbenzodiazepine HypnoticsShort-term treatment of insomniaadults
Etizest MDConsernetizolamBenzodiazepine analog/thienotriazolodiazepineShort-term treatment of anxiety and insomnia-
FazaCloAzurPharmayesclozapineAntipsychoticsTreatment-resistant schizophreniaadults
FluimucilAlpex Pharma SA / Zambon GroupN-acetylcysteineMucolyticCold and Cough16 years+
Jr. Tylenol MeltawaysMcNeil Consumer HealthcareyesacetaminophenAnalgesics, AntipyreticsPain, Fever6 years+
KemstroUCB Inc.nobaclofenMuscle relaxant, Antispastic
Klonopin WafersRocheyesclonazepamBenzodiazepines, Anticonvulsant, AnxiolyticsSeizure disordersinfants+
Klonopin WafersRocheyesclonazepamBenzodiazepines, Anticonvulsant, AnxiolyticsPanic disorderadults
Lamictal ODTAptalis / GlaxoSmithKlineyeslamotrigineAnticonvulsant, Mood stabilizerSeizure disorders2 years+
Lamictal ODTAptalis / GlaxoSmithKlineyeslamotrigineAnticonvulsant, Mood stabilizerBipolar I disorderadults
Maxalt-MLTMerck & Co.yesrizatriptanTriptans, Serotonin agonistsMigraineadults
meloxicam orodispersible tabletsAlpex Pharma Ltd ; Fontus Health Ltd meloxicamNSAIDsOsteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis16 years+
NiravamSchwarz PharmayesalprazolamBenzodiazepines, AnxiolyticsAnxiety disorder, Panic disorderadults
NocdurnaFerring PharmaceuticalsdesmopressinAntidiureticNocturiaadults
NuLevAlaven Pharmaceuticalhyoscyamineanticholinergic / antispasmodicPeptic ulcer, Symptoms of various gastrointestinal and urinary disorders2 years+
Nurofen MeltletsReckitt BenckiseribuprofenNSAIDsPain, Fever, Inflammation12 years+
Orapred ODTSciele PharmayesprednisoloneCorticosteroidsAsthma, Severe allergy, Hemolytic anaemia, Stevens–Johnson syndrome, Certain types of tuberculosis; acute treatment of arthritis, Bursitis, COPD, Leukemia, Lupus, Multiple sclerosis, Ulcerative colitisadults and children weighing over 44 lbs/20.1 kg
ParcopaSchwarz Pharmayescarbidopa/levodopaDDC inhibitors , Dopamine precursor Parkinson's diseaseadults
Pepcid RPDScherer DDS / MerckyesfamotidineHistamine H2-receptor antagonistsduodenal ulcer, gastric ulcer, gastroesophageal reflux disease, pathological hypersecretory conditionsadults
Prevacid SoluTabTakeda PharmaceuticalsyeslansoprazoleProton pump inhibitorsGastro-oesophageal reflux disease, Ulcers1 year+
Propulsid Quicksolv Janssen PharmanocisaprideGastroprokinetic agent
Reglan ODTMeda Pharms, Schwarz PharmayesmetoclopramideAntiemetics, Dopamine receptor antagonistsshort-term therapy for GERD, acute diabetic gastric stasisadults
Remeron SolTabMerck & Co.yesmirtazapineAntidepressantsMajor depressive disorderadults
Risperdal M-TabJanssen PharmayesrisperidoneAtypical antipsychoticsSchizophrenia13 years+
Risperdal M-TabJanssen PharmayesrisperidoneAtypical antipsychoticsBipolar disorder10 years+
Risperdal M-TabJanssen PharmayesrisperidoneAtypical antipsychoticsIrritability associated with autistic disorder5 years+
Rybix ODTVictory PharmayestramadolOpioid, SNRIPain16 years+
SaphrisMerck & Co.noasenapineAtypical antipsychoticsSchizophrenia, Bipolar disorderadults
StaxynBayer HealthcareyesvardenafilPhosphodiesterase 5 inhibitorErectile dysfunctionadult males
Striant BuccalColumbia LaboratoriesnotestosteroneAndrogen, Steroid hormoneHypogonadism adult males
Suboxone tablets Reckitt BenckisernoBuprenorphine/Naloxonesemi-synthetic opioid partial opioid agonist & inverse opioid antagonist
Opioid addictionadults
SuprenzaAlpex Pharma / CitiusnophentermineAmphetamines, AnorecticWeight controladults
Ultram ODTOrtho-McNeil PharmaceuticalyestramadolOpioid, SNRIPain17 years+
Unisom SleepMeltsChattemyesdiphenhydramineAntihistamines, HypnoticInsomnia12 years+
Vometa FTDexamedicadomperidoneAntiemetics, Prokinetic agentDyspepsia, Bloating, GERD, Gastroparesis12 years+
ZelaparValeant Pharmaceuticals InternationalnoselegilineMonoamine oxidase B inhibitors Adjunct therapy in parkinson's diseaseadults
Zofran ODTGlaxoSmithKlineyesondansetronAntiemeticsNausea, Vomiting4 years+
Zomig-ZMTAstraZenecayeszolmitriptanTriptans, Serotonin agonistsMigraineadults
Zyprexa ZydisEli Lilly and CompanyyesolanzapineAtypical antipsychoticsBipolar disorder, Schizophreniaadults
ZyrtecJohnson & Johnson Consumer Inc.,yescetirizineAntihistaminesAllergy

Advantages of ODTs

Ved Parkash et al. note the following advantages of ODTs:
Ved Parkash et al. lists the following disadvantages of ODTs: