Orally disintegrating tablet

Source: Wikipedia, the free encyclopedia.
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)

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

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

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 name Manufactured by/for Generic available[23] Active ingredient Category Indication Intended age
Abilify Discmelt[24]
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]
Adzenys XR-ODT Neos Therapeutics no amphetamine Amphetamines, Stimulants Attention deficit hyperactivity disorder 6 years+[25]
Alavert Quick Dissolving Tablets Wyeth yes loratadine Antihistamines Allergy 6 years+
Allegra ODT
Sanofi Aventis
yes fexofenadine Antihistamines
Urticaria[1]
6–11 years[1][26]
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[27] escitalopram Major depressive disorder, Generalized anxiety disorder, Obsessive–compulsive disorder adults[28]
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
Central diabetes insipidus
5 years+[29]
Edluar Meda AB yes zolpidem Nonbenzodiazepine Hypnotics Short-term treatment of insomnia[30] adults
Etizest MD Consern etizolam Benzodiazepine analog/thienotriazolodiazepine Short-term treatment of anxiety and insomnia
FazaClo AzurPharma yes clozapine Antipsychotics Treatment-resistant schizophrenia[31] adults[31]
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[32]
Roche
yes clonazepam Benzodiazepines, Anticonvulsant, Anxiolytics
Seizure disorders[32]
infants+[32]
Panic disorder[32] adults[32]
Lamictal ODT
GlaxoSmithKline
yes lamotrigine Anticonvulsant, Mood stabilizer
Seizure disorders
2 years+
Bipolar I disorder adults
Maxalt-MLT Merck & Co. yes rizatriptan 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[33]
Nocdurna Ferring Pharmaceuticals desmopressin Antidiuretic Nocturia adults[34]
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 adults and children weighing over 44 lbs/20.1 kg[6]
Parcopa
Schwarz Pharma
yes carbidopa/levodopa
Dopamine precursor
[levodopa]
Parkinson's disease[7] adults[7]
Pepcid RPD Scherer DDS / Merck yes famotidine
Histamine H2-receptor antagonists[35]
, pathological hypersecretory conditions adults
Prevacid SoluTab
Takeda Pharmaceuticals
yes lansoprazole
Proton pump inhibitors[8]
Ulcers[8]
1 year+[8]
Propulsid Quicksolv (withdrawn)
Janssen Pharma
no cisapride
Gastroprokinetic agent
Reglan ODT
Schwarz Pharma[36]
yes metoclopramide
Dopamine receptor antagonists
short-term therapy for GERD, acute diabetic gastric stasis[36] 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]
autistic disorder[9]
5 years+[9]
Rybix ODT Victory Pharma yes[37] tramadol Opioid, SNRI Pain 16 years+
Saphris Merck & Co. no[38] 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[37] tramadol Opioid, SNRI Pain 17 years+[39]
Unisom SleepMelts Chattem yes diphenhydramine Antihistamines, Hypnotic Insomnia 12 years+[40]
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[41]
Zofran ODT
GlaxoSmithKline
yes ondansetron Antiemetics Nausea, Vomiting[5] 4 years+[5]
Zomig-ZMT AstraZeneca yes zolmitriptan Migraine[11] adults[11]
Zyprexa Zydis Eli Lilly and Company yes olanzapine Atypical antipsychotics Bipolar disorder, Schizophrenia[42] adults [42]
Zyrtec Johnson & Johnson Consumer Inc., yes cetirizine Antihistamines Allergy[43]

Advantages of ODTs

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

Disadvantages of ODTs

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

  • unpleasant taste;

ODTs under development

Brand name
(generic version)
Manufacturer Active ingredient Category Indication Intended age
citalopram ODT[45] Biovail[45] citalopram
Major depressive disorder[46]
tramadol/acetaminophen ODT[45] Biovail[45]
acetaminophen
Opioid / non-opioid analgesic[47] Pain[45] adults[47]

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. ^ a b c Allegra Prescribing Information
  2. ^ a b c d "Aricept Prescribing Information" (PDF). Archived from the original (PDF) on 2008-09-10. Retrieved 2009-01-10.
  3. ^ a b c Maxalt Prescribing Information
  4. ^ a b c "Remeron SolTob Prescribing Information" (PDF). Archived from the original (PDF) on 2016-03-03. Retrieved 2009-01-10.
  5. ^ a b c "Zofran Prescribing Information" (PDF). Archived from the original (PDF) on 2014-02-02. Retrieved 2009-01-09.
  6. ^ a b c Orapred Prescribing Information
  7. ^ a b c Parcopa Prescribing Information
  8. ^ a b c d "Prevacid Prescribing Information" (PDF). Archived from the original (PDF) on 2009-09-20. Retrieved 2009-01-09.
  9. ^ a b c d e f g "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. ^ a b c "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.). 2016. Retrieved April 4, 2016.
  24. ^ a b c d e f g Abilify Prescribing Information Archived 2010-03-31 at the Wayback Machine
  25. ^ "Adzenys XR-ODT Prescribing Information" (PDF). Food and Drug Administration. January 2016. Retrieved 14 March 2016.
  26. ^ "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.
  27. ^ "Product Monograph: Act Escitalopram ODT" (PDF). Health Canada. 25 October 2016. Retrieved 16 August 2018.
  28. ^ "Product Monograph: Cipralex and Cipralex METLZ" (PDF). Health Canada. 9 June 2016. Retrieved 16 August 2018.
  29. ^ "Product Monograph: DDAVP Melt" (PDF). Ferring Pharmaceuticals Canada. 17 December 2015. Archived from the original (PDF) on 14 March 2016. Retrieved 14 March 2016.
  30. ^ Edluar Prescribing Information
  31. ^ a b FazaClo Prescribing Information
  32. ^ a b c d e "Klonopin Prescribing Information" (PDF). Archived from the original (PDF) on 2007-03-17. Retrieved 2009-01-10.
  33. ^ "Niravam - FDA prescribing information, side effects and uses".
  34. ^ "Product Monograph: Nocdurna" (PDF). 3 September 2014. Retrieved 14 March 2016.
  35. ^ "Pepcid (label)" (PDF). Food and Drug Administration. Retrieved April 4, 2016.
  36. ^ a b FDA Drug Approval for Reglan ODT
  37. ^ a b "FDA Issues Approval Letter For Tramadol ODT, for Moderate to Severe Pain". DocGuide. Retrieved 2016-04-04.
  38. ^ "Generic Saphris Availability - Drugs.com". www.drugs.com. Retrieved 2016-04-04.
  39. ^ "Ultram ODT - FDA prescribing information, side effects and uses". www.drugs.com. Archived from the original on 2016-04-04. Retrieved 2016-04-04.
  40. ^ "Unisom Drug Facts". Archived from the original on 2016-03-04. Retrieved 2009-01-14.
  41. ^ "Zelepar Prescribing Information" (PDF). July 2014. Retrieved 14 March 2016.
  42. ^ a b Zyprexa Prescribing Information
  43. ^ "ZYRTEC® Dissolve Tabs". ZYRTEC®. Retrieved 2016-04-04.
  44. ^
    PMID 22247889
    .
  45. ^ a b c d e "Biovail Product Pipeline". Archived from the original on 2009-09-15. Retrieved 2009-01-10.
  46. ^ Citalopram Prescribing Information
  47. ^ a b "Ultracet Prescribing Information" (PDF). Archived from the original (PDF) on 2011-06-05. Retrieved 2009-01-10.