Lec 20- MR systems- ODT

Question 1

Terminology

Answer 1

• Fast-dissolving
• Orodispersible- hypo-Salivation can lead to poor dissolving
• Fast-melting
• Orally dissolving- Needs to disintegrate in under 3 minutes
• FDA has adopted the term
  
  • Orally disintegrating tablets (ODT’s)

Question 2

Orally disintegrating tablets

Answer 2

• Advantages
  
  • Administration to patients who cannot, should not or will not swallow
    
    • Children, elderly, vets, stroke patient
  • Convenience (no water needed)
  • Taste masking is crucial-superior taste
  • Rapid intervention
  • Altered absorption profile
    
    • In solution when reach stomach or buccal absorption
      
      • Decreased onset time
      • Enhanced bioavailability
    • New business opportunity

Question 3

Bioavailability

Answer 3

• Some tablets are designed to dissolve in saliva remarkably fast, within a few seconds and are true fast-dissolving tablets
• Others contain agents to enhance the rate of tablet disintegration in the oral cavity and are more appropriately termed fast-disintegrating tablets as they may take up to 1 minute to completely disintegrate
• Increased bioavailability using such formulations is possible if there is sufficient absorption via the oral cavity prior to swallowing
• If the amount of swallowed drug varies
  
  • There is the potential for inconsistent bioavailability

Question 4

Challanges

Answer 4

• Taste- masking is crucial
  
  • Flavouring agent- spray drying
• Dose
• Moisture sensitivity- we normally have to use hygroscopic materials
  
  • Excessive water: microbial contamination, drug stability, disintegration of the tablet (or just weakness)
• Friability- low compression means tha
• High prosit, low density low hardnes
• Taste masking is crucial

Question 5

Technologies

Answer 5

• Zydis
• Orasolv/Durasolv
• Flashdose
• Flashtab
• Wowtab

Question 6

Zydis

Answer 6

• Freeze-drying methods
• Suspend excipients in liquid and freeze
• Sublimation then occurs (going from a solid to a gas without the liquid stage)- this will leave behind poors- encouraging disintegration- this is done by lowering the pressure
  
  • Zydis
    
    • E.g. lorazepam, piroxicam, loperamide, loratidine, enalapril, selegiline
  • Ideal for poorly water-soluble drugs
  • Water-insoluble
    
    • Dose<400mg, size<100um, acceptable taste
  • Water soluble
    
    • Dose- <500mg, acceptable taste, high eutectic temperature- the higher this point the easier it is to freeze this dosage form

Question 7

Composition

The matrix consists of

Answer 7

1. Water soluble polymer (gelatine, dextran or alginate)
   
   • Give the shape and resilience of the tablets
2. Saccharide (mannitol or sorbitol)- mouth feel
   
   • Give crystallinity, hardness and elegance
3. Lyoprotectant (Glycine)
   
   • Protects against collapsing of tablets during freeze drying- because we have to increase the temperature after freezing which can breakdown due to heat, this stops this
4. Other excipients (flavours, sweeteners and colouring agents)

Question 8

Zydis

preparation

Answer 8

• Preparation
  
  • Solution of polymer and saccharide in water
  • Drug suspended or dissolved in carrier solution
  • Precise dosing into pre-formed blisters
  • Frozen in liquid nitrogen
  • Rapidly freeze-dried
  • Heat-seal process for blisters to ensure stability and protect the fragile tablet during removal by the patient
• Complex nature of manufacture and scale up results in a relatively high manufacturing cost

Question 9

Zydis

Answer 9

• Porous matrix
  
  • Network of water-soluble carriers
  • Active ingredient
• Microencapsulation and complexation with ion-exchange resins can be used along with other flavours and sweeteners for taste-masking for bitter drugs

Question 10

Characterisation

Answer 10

• Successful tablet formulation must have adequate mechanical strength
  
  • The tablet dosage forms are exposed to various mechanical stresses during the manufacturing steps (e.g. packaging process), shipping and handling by patients
• Conventional tablets are usually assessed in terms of hardness and friability
  
  • Do you think the same can be used for freeze-dried tablets

Question 11

Flashdose

Answer 11

• Modified tabletting technology
  
  • Granulation of a low moldable sugar with a high moldable sugar to produce a fast disintegrating formulation
  • The inclusion of effervescing agents using microparticulate systems
  • Expensive
  • Formulations are friable and moisture sensitive, therefore requiring specialized packaging

Question 12

Tablet compression

Answer 12

• Durasolv (Cima Labs) and Ziplets (Eurand)
• Excipients play a major role in the successful formulation and uperdisintegrants, hydrophilic polymers and effervescent compounds are included
• Effective taste-masking is required for ALL formulation

Question 13

Tablet compression

Answer 13

• Blending and compression of excipients- e.g. direct compression
• Dry granulation e.g. roller compaction
• Wet granulation

Question 14

Therapeutic area’s

Answer 14

• PPI (e.g. Zoton Fastab®)
• Migraine (e.g.Maxalt Melt®, Zomig Rapimelt®)
• Reflux (e.g.Pepcid®, Propulsid®, Domperidone®)
• Antihistamine/antiemetic (e.g.Zofran®, Clarityn®)
• Analgesia/NSAID (e.g.Calpol®, Feldene®, Zamadol melt®)
• Antidiarrhoeal (e.g.Imodium®)
• Antipyschotic (e.g.Risperdal Quicklet)

Question 15

Maxalt melt

Answer 15

• Convenient (Fast) relief of migraine
  
  • In addition to tablets, nasal spray and injection
• Rizatriptan (10mg) in wafer
  
  • Without liquids
  • To reduce risk of nausea
  • Oral lyophilisates
    
    • Contain gelatin mannitol, glycine, aspartame, peppermint

Question 16

Zomig Rapimelt

Answer 16

• Rapid and long lasting
• AstraZeneca with CIMA
• Contain zolmitriptan in OraSolv technology
  
  • Taste masking

Question 17

Zomig Rapimelt

Answer 17

Question 18

Counselling

Answer 18

• The majority of patients receiving ODT preparations have little understanding of this new dosage form
• Pharmacists are in the ideal position to become familiar with the different technologies and educate their patients on what to expect upon taking their first dose
• Patients may be surprised when tablets begin to dissolve in the mouth. They might expect a faster onset of therapeutic action
  
  • Clarification from the pharmacist can avoid any confusion or misunderstanding

Question 19

Zyprexa Zydis/ Velotab

Answer 19

• 10,15 and 20mg olanzipine in orally disintegrating tablets
• Patient instructions
  
  • To use Zyprexa Velotab, open the sachet, peel back the foil on the blister pack, remove the tablet, and place the entire tablet in the mouth
  • Do not push the tablet through the foil
  • The medication can be taken with or without water; the saliva in your mouth will cause the tablet to dissolve

Question 20

Counselling

Answer 20

• Patients who concurrently take anticholinergic medications may not be the best candidates for this formulation
  
  • Decreased volume of saliva may slow the rate of dissolution/disintegration and decrease the bioavailability of the product