1. Evaluation Seminar A Review” “Fast Dissolving Tablets: PRESENTED BY :
ARUN PRATAP SINGH M.PHARM- II (DEPT OF P’CEUTICS)
K.L.E.S College of Pharmacy, Hubli

2. CONTENTS Introduction.
Advantages of an Fast dissolving drug delivery system.
Characteristics of an Ideal FDDDS.
Choice of drug candidate.
Basic approaches to develop FDDDS.
Techniques in preparation of orally disintegratingdrug delivery system.
List of Patented technologies.
References.

3. Introduction
United States Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) define orally disintegrating tablets in the ‘Orange Book’ as
“A solid dosage form which contain a medicinal substance or active ingredient which disintegrates rapidly within a matter of seconds when placed upon a tongue” .
European Pharmacopoeia described orally disintegrating tablets as “uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed’ and as tablets which should disintegrate within 3 min”.
APPROVED DRUG PRODUCTS WITH THERAPEUTIC EQUIVALENCE EVALUATIONS “Orange Book”

4. Advantages of an Fast dissolving drug delivery system
Improved patient compliance.
Rapid onset of action and may offer an improved bioavailability.
Useful for pediatric, geriatric and psychiatric patients.
Suitable during traveling where water is may not be available.
No specific packaging required, can be packaged in push through blisters.
Smooth mouth feel and pleasant taste.
Conventional manufacturing equipment.
Cost effective.
Good chemical stability as conventional oral solid dosage form.

5. Characteristics of an Ideal FDDDS
Utilizes cost effective production method.
Require no water for oral administration.
Dissolve / disperse/ disintegrate in mouth in a matter of seconds.
Have a pleasing mouth feel and taste masking.
Less friable and have sufficient hardness.
Leave minimal or no residue in mouth after administration.
Manufacturing using conventional manufacturing method.

6. Choice of drug candidate
No bitter taste.
Good stability in water and saliva.
Dose should be low as possible.
Unsuitable drug candidate for orally disintegrating tablet should include:
Short half-life and frequent dosing.
Drug having very bitter taste.
Required controlled or sustained release.

7. (dissolution limited) II
Dose/solubility ratio
250
500
1000
5000
10000
100000 I
Good solubility and permeability 10
(dissolution limited) II
Good permeability, poor solubility
(solubility limited absorption) 1
III
Good solubility, poor permeability IV
Poor solubility and permeability
0.1
BCS plot

8. API Properties – Biopharmaceutical Classification Scheme
Class I – high solubility, high permeability
- rapid absorption, good bioavailability
- eg propanolol, metaprolol
Class II – low solubility, high permeability
- particle size effects on bioavailability
- eg ketoprofen, carbamazepine
Class III high solubility, low permeability
- APIs dissolve rapidly and poorly absorbed
- require fast API dissolution to maximise absorption
- particle size reduction
eg ranitidine, atenolol
Class IV low solubility, low permeability
- challenging molecules, likely to exhibit low bioavailability
eg hydrochlorothiazide, furosemide,
- option to increase permeability - modify APIs as ‘prodrugs’

9. Basic approaches to develop FDDDS
porous structure
highly water-soluble
excipients
appropriate disintegrating agents
FDDDS 27 9

10. - Physical blending method - Kneading method
- Milling / Co-grinding technique Co-precipitation technique
- Solution/ solvent evaporation method Neutralization precipitation method
- Atomization/Spray drying method Supercritical antisolvent technique
- Microwave irradiation method
The degree of crystal damage can be directly correlated with the energy of the milling process.

11. API Properties Particle size, drug dissolution and bioavailability
Dissolution related to particle size and particle surface area
(smaller particle size, larger surface area, faster dissolution)
= dissolution rate, A = surface area of solid, k = dissolution
rate constant, Cs = saturation of drug, C = concentration of drug in solution)
API stability, solubility (dissolution) and particle size are key properties for effective formulation design

12. Techniques in preparation of Fast dissolving drug delivery system.
1. Freeze drying or Lyophilization
2. Spray Drying
3. Direct Compression
4. Sublimation
5. Cotton Candy Process
6. Mass Extrusion
7. Moulding
8. Nanonization
9. Fast Dissolving Films
10. Phase transition process
11. Melt granulation

13. Freeze drying or Lyophilization
Lyophilization means drying at low temperature under condition that involves the removal of water by sublimation. Drug in a water soluble matrix which is then freeze dried to give highly porous structure. The tablets prepared by lyophilization disintegrate rapidly in less than 5 seconds due to quick penetration of saliva in pores when placed in the oral cavity. Lyophilization is useful for heat sensitive drugs i.e. thermo-labile substances
Ex. Loratidine (Claritin Reditab and Dimetapp Quick Dissolve)
• Spray drying
Spray drying can produce highly porous and fine powders that dissolve rapidly. This technique is based on a particulate support matrix, which is prepared by spray drying an aqueous composition containing support matrix and other components to form a highly porous and fine powder. This then mixed with active Ingredients and compressed into tablets
Ex. Hyoscyamine Sulfate ODT

14. Freeze drying or Lyophilization

15. “Spray drying”

16. • Sublimation Direct compression
This is most popular technique because of its easy implementation and cost-effectiveness. The basic principle involves addition of disintegrants and/or water soluble excipients and/or effervescent agents. Superdisintegrants in optimum concentration (about 2- 5%) are mostly used so as to achieve rapid disintegration along with the good mouth feel.
Ex. Paracetamol (Tempra Quicklets), Zolmitriptan (Zolmig Repimelt)
• Sublimation
This technique is based on the use of volatile ingredients (e.g. camphor, ammonium bicarbonate, naphthalene, urea, urethane etc.) to other tablet excipients and the mixture is then compressed into tablets. Entrapped volatile material is then removed via sublimation, which leads to formation of a porous structure.
Ex. Phloroglucinol Hydrate (Spasfon Lyoc)

17. MANUFACTURING STEPS FOR DIRECT COMPRESSION

18. Steps Involved in sublimation

19. Cotton candy process - involves the formation of matrix of polysaccharides by simultaneous action of flash melting and spinning. This candy floss matrix is then milled and blended with active ingredients and excipients after re-crystallization and subsequently compressed to FDT.
Characteristics: It can accommodate high doses of drug and offers improved mechanical strength
Ex- Tramadol HCl (Relivia Flash dose)
Mass-Extrusion - involves softening the active blend using the solvent mixture of water soluble polyethylene glycol, methanol and expulsion of softened mass through the extruder or syringe to get a cylindrical shape of the product into even segments using heated blade to form tablets.
Characteristics: The dried product can be used to coat granules of bitter tasting drugs and thereby masking their
bitter taste.
Ex. Zolmitriptan (Zolmig ZMT)

20. Moulding - water-soluble ingredients with a hydro-alcoholic solvent is used and is molded into tablets under pressure lower than that used in conventional tablet compression.
Characteristics: Molded tablets are very less compact than compressed tablet porous structure that enhances
disintegration/dissolution and finally absorption increased.
Nanonization - involves size reduction of drug to nanosize by milling the drug using a proprietary wet-milling technique. The
nanocrystals of the drug are stabilized against agglomeration by surface adsorption on selected stabilizers, which are then incorporated into FDTs.
Characteristics: It is used for poorly water soluble drugs. It leads to higher bioavailability and reduction in dose, cost effective manufacturing process, conventional packaging due to exceptional durability and wide range of doses (up to 200 mg of drug per unit).

21. Ing. and Tech. Used for Formulating FDT:
Drug
Disint.Agents
Other form. Ing.
Tech. used
Disint. Time
NSAIDS
Crospovidone
(intragranula &
Extragranular)
Mcc,Aerosil, Mag.
stearate, stearic acid
Wet granulation & Direct
Compression
50 sec
(for 125 mgTab.)
Sildenafil granules
Cross linked povidone
Lemon flavor, aspartame,
mannitol
Freeze drying
< 30 sec
Ascorbic acid
Avicel ph 101
Pregelatinized starch,
Moulding, Direct
31-37 sec

22. List of Patented technologies.
The various technologies are developed for the of Orally Disintegrating
Drug Delivery System that are:
1) Zydis (Lyophilization) ) Lyoc (Multiparticulate Compressed tab.)
3) Wowtab(Comp. Molded Tab.) ) Flashtab (Lyophilization)
5) Durasolv (Moulding) ) Orasolv (Compressed Tablets)
7) Flashdose(Cotton-candy process) 8) OraQuick (Micromask taste Masking)
9) Ziplets (Moulding) ) Fast Melt (Moulding)

23. - Preformulation studies of fast dissolving tablets :-
Bulk Density (Db)
Tapped Density (Dt)
Angle of Repose
Powder flow properties - Carr’s index (or) % compressibility
Hausner ratio
- Identification of drug sample and Drug excipient
Compatibility study: by FTIR(KBr pellet method) and DSC
- Evaluation test for fast dissolving tablets:
General Appearance Weight variation
Hardness Friability (F)
Drug Content Wetting time & Water absorption Ratio
In-Vitro drug release Powder X-ray diffraction
Modified disintegration test In-vitro dispersion time
Moisture uptake study Stability study

24. Disintegration Test using Modified Dissolution Apparatus

25. Limitations of Mouth Dissolving Tablets
The tablets usually have insufficient mechanical strength. Hence, careful handling is required.
The tablets may leave unpleasant taste and/or grittiness in mouth if not formulated properly.
Drugs with larger doses are difficult to formulate into FDT e.g. rifampin (600 mg), ethambutol (1000mg) etc.

26. List of commercially Available Fast dissolving tablets
Manufacturer
Trade Name
Active Drug
Felden fast melt
Claritin redi Tab
Maxalt MLT
Zyprexia
Pepcid RPD
Zofran ODT
Zoming-ZMT
Zeplar TM
Tempra Quiclets
Febrectol
Nimulid MDT
Torrox MT
Olanex instab
Romilast
Benadryl Fastmelt
Piroxicam
Loratidine
Rizatriptan
Olanzapine
Famotidine
Ondansetron
Zolmitriptan
Selegilline
Acetaminophen
Paracetamol
Nimesulide
Rofecoxib
Montelukast
Diphenhydramine
and pseudoephedrine
Pfiser Inc., NY, USA
Schering plough Corp., USA
Merck and Co., NJ, USA
Eli lilly, Indianapolis, USA
Glaxo Wellcome, Middlesex, UK
AstraZeneca, Wilmington, USA
Amarin Corp., London, UK
Bristol myers Squibb, NY, USA
Prographarm, Chateauneuf, France
Panacea Biotech, New delhi , India
Torrent pharmaceuticals , India
Ranbaxy lab. Ltd. New-delhi, India
Warner Lambert, NY, USA

27. Industrial Applications
Industrial applications include the following:
To develop an orally disintegrating dosage forms and to work with existing disintegrants
To further improvise upon the existing technology of ODTs
To optimize the blend of disintegrants or excipients to achieve ODTs
To select and develop proper packaging material and system for enhanced stability of the product and also develop a cost-effective product
To arrive at various taste-masking agents and prepare palatable dosage forms thereby increasing patient compliance
To develop disintegrants from different polymers which are used as coating materials by certain modifications and use them for formulating ODTs

28. References
Virely P, Yarwood R. Zydis - a novel, fast dissolving dosage form.
Manuf Chem. 1990; 61: 36–37.
Watanabe Y.New compressed tablet rapidly disintegrating in the mouth using crystalline cellulose and adisintegrant.Biol Pharm Bull. 2004; 18: 1308–1310
Koizumi KI, Watanabe Y, Morita K, Utoguchi N, Matsumoto M.New method for preparing high porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material.Int J Pharm. 2009; 152: 127–131.
Dali Shukla, Subhashis Chakraborty, Sanjay singh, Brahemeshwar mishra. Mouth dissolving tablet I: An overview of formulation technology. Scientica Pharmaceutica. 2009; 77:
Jaysukh J Hirani, Dhaval A Rathod, Kantilal R Vadalia. Orally disintegrating tablets: A Review. Tropical Journal of Pharmaceutical Research. 2009; 8(2):

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