Orally disintegrating tablet

clonazepam ODT blister pack and tablet
Etizest-1 MD (Etizest-brand 1mg-doskk etizolam mouth-dissolving (MD) blister pack and opened tablet

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.[1][2][3][4][5][6][7][8][9][10][11] 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 [12][13] and 18-22% of all patients in long-term care facilities [14] 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.[15] 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.[16] 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.[17] 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).[18] 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.[19] It was followed by a Zydis ODT formulation of Klonopin (clonazepam) in December 1997,[20] and a Zydis ODT formulation of Maxalt (rizatriptan) in June 1998.[21] 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.[22] 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 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 (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/for Generic available[23]Active ingredientCategoryIndicationIntended age
Abilify Discmelt[24] Otsuka America/Bristol-Myers Squibb yes aripiprazole Atypical antipsychotics Schizophrenia[24] 13 years+[24]
Bipolar disorder[24] 10 years+[24]
Adjunct therapy for major depressive disorder[24] adults[24]
Abstral Sentynl Therapeutics fentanyl Opioid Breakthrough pain in persons with cancer adults[25]
Adzenys XR-ODT Neos Therapeutics no amphetamine Amphetamines, Stimulants Attention deficit hyperactivity disorder 6 years+[26]
Alavert Quick Dissolving Tablets Wyeth yes loratadine Antihistamines Allergy 6 years+
Allegra ODT Sanofi Aventis yes fexofenadine Antihistamines Allergic rhinitis, Urticaria[1] 6–11 years[1][27]
Aricept ODT Eisai Co. yes donepezil Acetylcholinesterase inhibitors[2] Alzheimer's disease[2] adults[2]
Benadryl FastMelt Pfizer yes diphenhydramine Antihistamines Allergy 6 years+
Calpol Fast Melts McNeil Healthcare UK yes paracetamol Analgesics Pain 6 years+
Cipralex MELTZ Lundbeck yes[28] escitalopram SSRIs, Antidepressant Major depressive disorder, Generalized anxiety disorder, Obsessive–compulsive disorder adults[29]
Clarinex RediTabs Schering-Plough yes desloratadine Antihistamines Allergy 6 years+
Claritin RediTabs Bayer yes loratadine Antihistamines Allergy 6 years+
DDAVP Melt Ferring Pharmaceuticals desmopressin Antidiuretic Bedwetting, Central diabetes insipidus 5 years+[30]
Edluar Meda AB yes zolpidem Nonbenzodiazepine Hypnotics Short-term treatment of insomnia[31] adults
Etizest MD Consern etizolam Benzodiazepine analog/thienotriazolodiazepine Short-term treatment of anxiety and insomnia
FazaClo AzurPharma yes clozapine Antipsychotics Treatment-resistant schizophrenia[32] adults[32]
Fluimucil Alpex Pharma SA / Zambon Group N-acetylcysteine Mucolytic Cold and Cough 16 years+
Jr. Tylenol Meltaways McNeil Consumer Healthcare yes acetaminophen Analgesics, Antipyretics Pain, Fever 6 years+
Kemstro UCB Inc. no baclofen Muscle relaxant, Antispastic
Klonopin Wafers[33] Roche yes clonazepam Benzodiazepines, Anticonvulsant, Anxiolytics Seizure disorders[33] infants+[33]
Panic disorder[33] adults[33]
Lamictal ODT Aptalis / GlaxoSmithKline yes lamotrigine Anticonvulsant, Mood stabilizer Seizure disorders 2 years+
Bipolar I disorder adults
Maxalt-MLT Merck & Co. yes rizatriptan Triptans, Serotonin agonists Migraine[3] adults[3]
meloxicam orodispersible tablets Alpex Pharma Ltd (UK); Fontus Health Ltd (UK) meloxicam NSAIDs Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis 16 years+
Niravam Schwarz Pharma yes alprazolam Benzodiazepines, Anxiolytics Anxiety disorder, Panic disorder adults[34]
Nocdurna Ferring Pharmaceuticals desmopressin Antidiuretic Nocturia adults[35]
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 Pharma yes 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 colitis[6] adults and children weighing over 44 lbs/20.1 kg[6]
Parcopa Schwarz Pharma yes carbidopa/levodopa DDC inhibitors [carbidopa], Dopamine precursor [levodopa] Parkinson's disease[7] adults[7]
Pepcid RPD Scherer DDS / Merck yes famotidine Histamine H2-receptor antagonists[36] duodenal ulcer, gastric ulcer, gastroesophageal reflux disease, pathological hypersecretory conditions adults
Prevacid SoluTab Takeda Pharmaceuticals yes lansoprazole Proton pump inhibitors[8] Gastro-oesophageal reflux disease (GERD), Ulcers[8] 1 year+[8]
Propulsid Quicksolv (withdrawn) Janssen Pharma no cisapride Gastroprokinetic agent
Reglan ODT Meda Pharms, Schwarz Pharma[37] yes metoclopramide Antiemetics, Dopamine receptor antagonists short-term therapy for GERD, acute diabetic gastric stasis[37] adults
Remeron SolTab Merck & Co. yes mirtazapine Antidepressants Major depressive disorder[4] adults[4]
Risperdal M-Tab Janssen Pharma yes risperidone Atypical antipsychotics Schizophrenia[9] 13 years+[9]
Bipolar disorder[9] 10 years+[9]
Irritability associated with autistic disorder[9] 5 years+[9]
Rybix ODT Victory Pharma yes[38] tramadol Opioid, SNRI Pain 16 years+
Saphris Merck & Co. no[39] asenapine Atypical antipsychotics Schizophrenia, Bipolar disorder adults
Staxyn Bayer Healthcare yes vardenafil Phosphodiesterase 5 (PDE5) inhibitor Erectile dysfunction adult males
Striant Buccal Columbia Laboratories no 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

(Naloxone is included because it deters abuse. Naloxone is poorly absorbed into the body when used by mouth or as an ODT. However, when the pill is crushed and/or filtered and injected intravenously, naloxone blocks the effects of buprenorphine.)

 Opioid addiction adults
Suprenza Alpex Pharma / Citius no phentermine Amphetamines, Anorectic Weight control adults
Ultram ODT Ortho-McNeil Pharmaceutical yes[38] tramadol Opioid, SNRI Pain 17 years+[40]
Unisom SleepMelts Chattem yes diphenhydramine Antihistamines, Hypnotic Insomnia 12 years+[41]
Vometa FT Dexamedica domperidone Antiemetics, Prokinetic agent Dyspepsia, Bloating, GERD, Gastroparesis 12 years+
Zelapar Valeant Pharmaceuticals International no selegiline Monoamine oxidase B inhibitors (MAOBIs) Adjunct therapy in parkinson's disease adults[42]
Zofran ODT GlaxoSmithKline yes ondansetron Antiemetics Nausea, Vomiting[5] 4 years+[5]
Zomig-ZMT AstraZeneca yes zolmitriptan Triptans, Serotonin agonists Migraine[11] adults[11]
Zyprexa Zydis Eli Lilly and Company yes olanzapine Atypical antipsychotics Bipolar disorder, Schizophrenia[43] adults [43]
Zyrtec Johnson & Johnson Consumer Inc., yes cetirizine Antihistamines Allergy[44]

Advantages of ODTs

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

  • they are easy to consume and as such are convenient for such patients as "the elderly, stroke victims, bedridden patients, patients affected by kidney failure, and people who refuse to swallow, such as pediatric, geriatric, and psychiatric patients";
  • increased bioavailability (rapid absorption) due to pregastric absorption;
  • don't require water to consume and thus suitable for "patient compliant for disabled, bedridden patients, and for travelers and busy people who do not always have access to water";
  • good mouth feel;
  • improved safety due to low risk of choking or suffocation during oral administration.[45]

Disadvantages of ODTs

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

  • unpleasant taste;
  • cost-intensive production process;
  • lack of physical resistance in standard blister packs;
  • limited ability to incorporate higher concentrations of active drug.[45]

ODTs under development

Brand name
(generic version)		 Manufacturer Active ingredient Category Indication Intended age
citalopram ODT[46] Biovail[46] citalopram SSRIs, Antidepressant Major depressive disorder[47]
tramadol/acetaminophen ODT[46] Biovail[46] tramadol / acetaminophen Opioid / non-opioid analgesic[48] Pain[46] adults[48]

See also

  • Phagophobia - fear of swallowing
  • Pnigophobia - fear of choking
  • Sugar alcohol - a family of chemicals common in ODTs to enhance the mouth feel of the tablet as it disintegrates

References

  1. 1 2 3 Allegra Prescribing Information
  2. 1 2 3 4 "Aricept Prescribing Information" (PDF). Archived from the original (PDF) on 2008-09-10. Retrieved 2009-01-10.
  3. 1 2 3 Maxalt Prescribing Information
  4. 1 2 3 "Remeron SolTob Prescribing Information" (PDF). Archived from the original (PDF) on 2016-03-03. Retrieved 2009-01-10.
  5. 1 2 3 "Zofran Prescribing Information" (PDF). Archived from the original (PDF) on 2014-02-02. Retrieved 2009-01-09.
  6. 1 2 3 Orapred Prescribing Information
  7. 1 2 3 Parcopa Prescribing Information
  8. 1 2 3 4 "Prevacid Prescribing Information" (PDF). Archived from the original (PDF) on 2009-09-20. Retrieved 2009-01-09.
  9. 1 2 3 4 5 6 7 "Risperdal Prescribing Information" (PDF). Archived from the original (PDF) on 2009-01-06. Retrieved 2009-01-10.
  10. ↑ "Zelapar Prescribing Information" (PDF). Archived from the original (PDF) on 2008-05-09. Retrieved 2009-01-09.
  11. 1 2 3 "Zomig Prescribing Information" (PDF). Archived from the original (PDF) on 2015-02-18. Retrieved 2009-01-09.
  12. ↑ Sastry, S. et al., Pharm. Sci. & Tech. Today 3: 138-145, 2000.
  13. ↑ Groher ME, Bukatman MS. The prevalence of swallowing disorders in two teaching hospitals. Dysphagia. 1: 3-6, 1986.
  14. ↑ Layne KA, Losinski DS, Zenner PM, Ament JA. Using the Fleming index of dysphagia to establish prevalence. Dysphagia. 4: 39-42, 1989.
  15. ↑ US 5073374, Mccarty, John A., "Fast dissolving buccal tablet", published 1991-12-17
  16. ↑ US 5223264, Wehling, Fred; Schuehle, Steve & Madamala, Navayanarao, "Pediatric effervescent dosage form", published 1993-06-29
  17. ↑ US 5178878, Wehling, Fred; Schuehle, Steve & Madamala, Navayanarao, "Effervescent dosage form with microparticles", published 1993-01-12
  18. ↑ US 4946684, Blank, Robert G.; Mody, Dhiraj S. & Kenny, Richard J. et al., "Fast dissolving dosage forms", published 1990-08-07
  19. ↑ FDA Drug Details for Claritin RediTabs
  20. ↑ FDA Drug Details for Klonopin Wafer
  21. ↑ FDA Drug Details for Maxalt-MLT
  22. ↑ FDA Guidance for Industry Orally Disintegrating Tablets
  23. ↑ "Approved Drug Products with Therapeutic Equivalence Evaluations" (PDF). Food and Drug Administration (36 ed.). Food and Drug Administration. 2016. Retrieved April 4, 2016.
  24. 1 2 3 4 5 6 7 Abilify Prescribing Information Archived 2010-03-31 at the Wayback Machine
  25. ↑ "Abstral Prescribing Information" (PDF). November 2014. Retrieved 14 March 2016.
  26. ↑ "Adzenys XR-ODT Prescribing Information" (PDF). Food and Drug Administration. January 2016. Retrieved 14 March 2016.
  27. ↑ "Allegra - FDA prescribing information, side effects and uses". www.drugs.com. Retrieved 2016-04-04. Allegra ODT is intended for use only in children 6 to 11 years of age.
  28. ↑ "Product Monograph: Act Escitalopram ODT" (PDF). Health Canada. 25 October 2016. Retrieved 16 August 2018.
  29. ↑ "Product Monograph: Cipralex and Cipralex METLZ" (PDF). Health Canada. 9 June 2016. Retrieved 16 August 2018.
  30. ↑ "Product Monograph: DDAVP Melt" (PDF). Ferring Pharmaceuticals Canada. 17 December 2015. Retrieved 14 March 2016.
  31. ↑ Edluar Prescribing Information
  32. 1 2 FazaClo Prescribing Information
  33. 1 2 3 4 5 "Klonopin Prescribing Information" (PDF). Archived from the original (PDF) on 2007-03-17. Retrieved 2009-01-10.
  34. ↑ "Niravam - FDA prescribing information, side effects and uses".
  35. ↑ "Product Monograph: Nocdurna" (PDF). 3 September 2014. Retrieved 14 March 2016.
  36. ↑ "Pepcid (label)" (PDF). Food and Drug Administration. Retrieved April 4, 2016.
  37. 1 2 FDA Drug Approval for Reglan ODT
  38. 1 2 "FDA Issues Approval Letter For Tramadol ODT, for Moderate to Severe Pain". DocGuide. Retrieved 2016-04-04.
  39. ↑ "Generic Saphris Availability - Drugs.com". www.drugs.com. Retrieved 2016-04-04.
  40. ↑ "Ultram ODT - FDA prescribing information, side effects and uses". www.drugs.com. Retrieved 2016-04-04.
  41. ↑ Unisom Drug Facts
  42. ↑ "Zelepar Prescribing Information" (PDF). July 2014. Retrieved 14 March 2016.
  43. 1 2 Zyprexa Prescribing Information
  44. ↑ "ZYRTEC® Dissolve Tabs". ZYRTEC®. Retrieved 2016-04-04.
  45. 1 2 Ved Parkash; et al. (2011). "Fast disintegrating tablets: Opportunity in drug delivery system". Journal of Advanced Pharmaceutical Technology & Research. 2 (4): 223–35. doi:10.4103/2231-4040.90877. PMC 3255350. PMID 22247889.
  46. 1 2 3 4 5 "Biovail Product Pipeline". Archived from the original on 2009-09-15. Retrieved 2009-01-10.
  47. ↑ Citalopram Prescribing Information
  48. 1 2 "Ultracet Prescribing Information" (PDF). Archived from the original (PDF) on 2011-06-05. Retrieved 2009-01-10.
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