Many techniques have been reported for the formulation of Fast dissolving tablets or Orodispersible tablets.

1. Freeze drying / lyophilization
2. Tablet Moulding
3. Spray drying
4. Sublimation
5. Direct compression
6. Mass extrusion
7. Melt granulation
8. Phase transition process
9. Cotton Candy Process


Freeze-Drying or Lyophilization 

Freeze drying is the process in which water is sublimed from the product after it is frozen. Freeze-dried forms offer more rapid dissolution than other available solid products. The lyophilization process imparts glossy amorphous structure to the bulking agent and sometimes to the drug, thereby enhancing the dissolution characteristics of the formulation.


The active drug is dissolved or dispersed in an aqueous solution of a carrier/polymer. The mixture is done by weight and poured in the walls of the preformed blister packs. The trays holding the blister packs are passed through liquid nitrogen freezing tunnel to freeze the drug solution or dispersion. Then the frozen blister packs are placed in refrigerated cabinets to continue the freeze-dryinG. After freeze-drying the aluminum foil backing is applied on a blister-sealing machine. Finally the blisters are packaged and shipped.

The freeze-drying technique has demonstrated improved absorption and increase in bioavailability. The major disadvantages of lyophillization technique are :
  • expensive and time consuming
  • fragility makes conventional packaging unsuitable for these products
  • poor stability under stress ed condition

 
Freeze Dryer
Commonly used excipients with their uses and examples employed in manufacturing of Oral Dispersible Tablet (ODT)/ Fast Dissolving Tablet(FDT) using Freeze drying are listed in this following table.



ExcipientsUseExamples
PolymerStrength and rigidityGelatin, alginate and dextrin
PolysaccharidesCrystallinity, hardness and palatabilityMannitol and sorbitol
Collapse protectantsPrevents shrinkingGlycerin
Flocculating agentsUniform dispersionXanthan gum and acacia
PreservativesPrevent micExcipienrobial and fungal growthParabens
Permeation enhancerTransmucosal permeability enhancerSodium lauryl sulphate
pH adjustersChemical stabilityCitric acid and sodium hydroxide
Flavours and sweetenersPatient compliance---
WaterPorous unit formation---


1.  Tablet Molding

Tablet produced by moulding are solid dispersion. Moulded tablets disintegrate more rapidly and offer improved taste because the dispersion matrix is in general made from water soluble sugars. The active ingredients in most cases are absorbed through the mucosal lining of the mouth.
Molding process is of two types i.e. solvent method and heat method. 

Solvent method involves moistening the powder blend with a hydro alcoholic solvent followed by compression at low pressures in molded plates to form a wetted mass (compression molding). The solvent is then removed by air-drying. Thus the process is similar to what is used in the manufacture of tablet triturates. Such tablets are less compact than compressed tablets and possess a porous structure that hastens dissolution.

The heat molding process involves preparation of a suspension that contains a drug, agar and sugar (e.g. mannitol or lactose) and pouring the suspension in the blister packaging wells, solidifying the agar at the room temperature to form a jelly and drying at 30C under vacuum. The heat-molding process uses an agar solution as a binder and a blister packaging well as a mold to manufacture a tablet.  The mechanical strength of molded tablets is a matter of great concern. Binding agents, which increase the mechanical strength of the tablets, need to be incorporated. Taste masking is an added problem to this technology. 

The taste masked drug particles were prepared by spray congealing a molten mixture of hydrogenated cottonseed oil, sodium carbonate, lecithin, polyethylene glycol and an active ingredient into a lactose based tablet triturate form. Compared to the lyophillization technique, tablets produced by the molding technique are easier to scale up for industrial manufacture. 

Moulded tablets usually are prepared from soluble ingredients by compressing a powder mixture previously moistened with solvent (usually ethanol or water) into mould plates to form a wetted mass (compression moulding). Recently, moulded forms also have been prepared directly from a molten matrix in which the drug is dissolved or dispersed (heat moulding) or by evaporating the solvent from a drug solution or suspension at standard pressure (no-vacuum lyophilization).

Tablets produced by moulding are solid dispersions. The physical form of the drug in the tablets depends on whether, and to what extent, it dissolves in the molten carrier. The drug can exist as discrete particles or microparticles dispersed in the matrix. It can dissolve totally in the molten carrier to form a solid solution, or dissolve partially in the molten carrier while the remaining particles stay undissolved and dispersed in the matrix. The characteristics of the tablets (such as disintegration time, drug dissolution rate, and mouth feel) will depend on the type of the dispersion or dissolution. Because the dispersion matrix is, in general, made from water soluble sugars, moulded tablets disintegrate more rapidly and offer improved taste. These properties are enhanced when tablets with porous structures are produced or when components that are physically modified by the moulding process are used. Unfortunately, moulded tablets typically do not possess great mechanical strength. Erosion and breakage of the moulded tablets often occurs during tablet handling and when blister pockets are opened. Hardness agents can be added to the formulation, but then the rate of tablet solubility usually decreases.

2.    Spray Drying 

Spray dryers are widely used in pharmaceuticals and biochemical processes. Due to processing solvent is evaporated rapidly; spray drying can produce highly porous, fine powder. Spray drying can be used to prepare rapidly disintegrating tablets. 

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 is then mixed with active ingredients and compressed into tablets.

Gelatin can be used as a supporting agent and as a matrix, mannitol as a bulking agent and sodium starch glycolate or crosscarmellose or crospovidone are used as superdisintegrants. Tablets manufactured from the spray-dried powder have been reported to disintegrate in less than 20 seconds in aqueous medium. The formulation contained bulking agent like mannitol and lactose, a Superdisintegrant like sodium starch glycolate & croscarmellose sodium and acidic ingredient (citric acid) and/or alkaline ingredients (e.g. sodium bicarbonate). This spray-dried powder, which compressed into tablets showed rapid disintegration and enhanced dissolution. 

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