Orally disintegrating tablet

clonazepam ODT blister pack and tablet

An orally disintegrating 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] During the last decade, ODTs have become available in a variety of therapeutic markets, both OTC and by prescription. An additional reason to use an ODTs is the convenience of a tablet that can be taken without water.

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.

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 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

Product: Manufactured By/For: Active ingredient: Category: Indication: Intended Age:
Abilify Discmelt[23] Otsuka America/Bristol-Myers Squibb Aripiprazole Atypical antipsychotics Schizophrenia, Bipolar disorder, adjunct therapy for Major Depressive Disorder[23] 13 years+ for Schizophrenia, 10 years+ for Bipolar disorder, adults for MDD[23]
Alavert Quick Dissolving Tablets Wyeth Loratadine Anti-histamines Allergy 6 years+
Allegra ODT Sanofi Aventis Fexofenadine Anti-histamines Allergic rhinitis, Urticaria[1] 6–11 years[1]
Aricept ODT Eisai Co. Donepezil Acetylcholinesterase inhibitors[2] Alzheimer's disease[2] adults[2]
Benadryl FastMelt Pfizer Diphenhydramine Anti-histamines Allergy 6 years+
Calpol Fast Melts McNeil Healthcare UK Paracetamol Analgesics Pain 6 years+
Clarinex RediTabs Schering-Plough Desloratadine Anti-histamines Allergy 6 years+
Claritin RediTabs Schering-Plough Loratadine Anti-histamines Allergy 6 years+
Clonazepam ODT Par Pharmaceutical Clonazepam Benzodiazepines Anxiety, Panic Disorder, Seizure Disorders[24] infants+[24]
Edluar Meda AB Zolpidem Nonbenzodiazepine Hypnotics Short-term treatment of Insomnia[25] Adults
FazaClo AzurPharma Clozapine Antipsychotics treatment-resistant Schizophrenia[26] adults[26]
Fluimucil Alpex Pharma SA / Zambon Group N-Acetylcysteine Mucolitic Cold and Cough Group over 16
Jr. Tylenol Meltaways McNeil Consumer Healthcare acetaminophen Analgesics, Anti-pyretics Pain, Fever 6 years+
Klonopin Wafers[27] Roche clonazepam Benzodiazepines Panic Disorder, Seizure Disorders[27] infants+ for seizure disorders, adults for Panic Disorder[27]
Lamictal ODT Aptalis / GlaxoSmithKline lamotrigine Anticonvulsant Bipolar I Disorder, Epilepsy 18+ for bipolar, 2+ for seizure
Loratadine Redidose Ranbaxy loratadine Antihistamines Allergy 6 years+
Maxalt-MLT Merck & Co. Rizatriptan Triptans/Serotonin agonists acute Migraine[3] 18 years+[3]
Meloxicam 7.5 & 15 mg Orodispersible Tablets Alpex Pharma (UK) LTD Meloxicam NSAIDs osteoarthritis,rheumatoid arthritis and ankylosing spondylitis 16 years+
Mirtazapine ODT Teva Pharmaceuticals Mirtazapine Antidepressants Major Depressive Disorder[4] adults[4]
Niravam Schwarz Pharma Alprazolam Benzodiazepines Anxiety, Panic Disorder Adults 18+[28]
Nurofen Meltlets Reckitt Benckiser Ibuprofen NSAIDs Pain, Fever, Inflammation 12 years+
Ondansetron ODT Teva Pharmaceuticals Ondansetron Antiemetics Nausea, Vomiting[5] 4 years+[5]
Orapred ODT Sciele Pharma 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 Carbidopa/levodopa DDC inhibitors [carbidopa] Parkinson's disease[7] adults[7]
Prevacid SoluTab Takeda Pharmaceuticals Lansoprazole Proton pump inhibitors[8] Gastro-oesophageal Reflux Disease (GERD), Ulcers[8] 1 year+[8]
Remeron SolTab Schering-Plough Mirtazapine Antidepressants Major Depressive Disorder[4] adults[4]
Risperdal M-Tab Janssen Risperidone Atypical antipsychotics Schizophrenia, Bipolar disorder, Irritability associated with Autistic disorder[9] 13 years+ for Schizophrenia, 10 years+ for Bipolar disorder, 5 years+ for Autism[9]
Saphris Merck & Co. Asenapine Atypical antipsychotics Schizophrenia, Bipolar disorder Adults
Striant Buccal Columbia Laboratories Testosterone Male Sexual Dysfunction
Suprenza www.alpex.com Alpex Pharma / Citius Phentermine Amphetamine Weight control Adults
UNISOM SleepMelts Aptalis / Chattem Diphenhydramine Anticholinergic Nighttime Sleep Aid Adults and children 12 years+[29]
VOMETA FT (Flash Tab) Dexamedica Domperidone Antimetics/Prokinetic Agent Dyspepsia, Bloating, GERD, Gastroparesis Adults and children 12 years old and above
Zelapar Valeant Pharmaceuticals Int'l Selegiline Monoamine oxidase inhibitors (MAOIs)[10] adjunct therapy in Parkinson's disease[10] adults[10]
Zofran ODT GlaxoSmithKline Ondansetron Antiemetics Nausea, Vomiting[5] 4 years+[5]
Zomig-ZMT AstraZeneca Zolmitriptan Triptans/Serotonin agonists Migraine[11] adults[11]
Zyprexa Zydis Eli Lilly and Company Olanzapine Atypical antipsychotics Bipolar disorder, Schizophrenia[30] adults [30]

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:

ODTs under development

Product Manufacturer Active ingredient Category Indication Intended Age Group
Citalopram ODT[32] Biovail[32] Citalopram SSRIs Major Depressive Disorder[33]
Metoclopramide Zydis[34] Salix Pharmaceuticals[34] Metoclopramide Dopamine receptor antagonists short-term therapy for GERD, acute diabetic gastric stasis[34] adults[34]
Reglan ODT[35] Schwarz Pharma[35] Metoclopramide Dopamine receptor antagonists short-term therapy for GERD, acute diabetic gastric stasis[35] adults[35]
Tramadol/Acetaminophen ODT[32] Biovail[32] Tramadol/Acetaminophen Opioid analgesic [Tramadol][36] Pain[32] adults[36]
Zolpidem ODT[32] Biovail[32] Zolpidem Nonbenzodiazepine Hypnotics[37] Sleep disorders[32] adults[37]

See also

References

  1. 1 2 3 Allegra Prescribing Information
  2. 1 2 3 4 Aricept Prescribing Information
  3. 1 2 3 Maxalt Prescribing Information
  4. 1 2 3 4 5 Remeron SolTob Prescribing Information
  5. 1 2 3 4 5 Zofran Prescribing Information
  6. 1 2 3 Orapred Prescribing Information
  7. 1 2 3 Parcopa Prescribing Information
  8. 1 2 3 4 Prevacid Prescribing Information
  9. 1 2 3 Risperdal Prescribing Information
  10. 1 2 3 4 Zelapar Prescribing Information
  11. 1 2 3 Zomig Prescribing Information
  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
  16. ↑ US 5223264, Wehling, Fred; Steve Schuehle & Navayanarao Madamala, "Pediatric effervescent dosage form", published 1993
  17. ↑ US 5178878, Wehling, Fred; Steve Schuehle & Navayanarao Madamala, "Effervescent dosage form with microparticles", published 1993
  18. ↑ US 4946684, Blank, Robert G.; Dhiraj S. Mody & Richard J. Kenny et al., "Fast dissolving dosage forms", published 1990
  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. 1 2 3 Abilify Prescribing Information
  24. 1 2 Clonazepam ODT Prescribing Information
  25. ↑ Edluar Prescribing Information
  26. 1 2 FazaClo Prescribing Information
  27. 1 2 3 Klonopin Prescribing Information
  28. ↑ http://www.drugs.com/pro/niravam.html
  29. ↑ Unisom Drug Facts
  30. 1 2 Zyprexa Prescribing Information
  31. 1 2 >Ved Parkash; et al. (2011). "Fast disintegrating tablets: Opportunity in drug delivery system". http://www.ncbi.nlm.nih.gov/. Journal of Advanced Pharmaceutical Technology & Research; 2011 Oct-Dec; 2(4). Retrieved 2014-00-01. Check date values in: |access-date= (help)
  32. 1 2 3 4 5 6 7 8 Biovail Product Pipeline
  33. ↑ Citalopram Prescribing Information
  34. 1 2 3 4 Salix Pharmaceuticals Acquires Patent–Protected Metoclopramide–Zydis
  35. 1 2 3 4 FDA Drug Approval for Reglan ODT
  36. 1 2 Ultracet Prescribing Information
  37. 1 2 Ambien Prescribing Information
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