Sublimation

To generate a porous matrix, volatile ingredients are incorporated in the formulation that is later subjected to a process of sublimation. Highly volatile ingredients like ammonium bicarbonate, ammonium carbonate, benzoic acid, camphor, naphthalene, urea, urethane and phthalic anhydride may be compressed along with other excipients into a tablet. This volatile material is then removed by sublimation leaving behind a highly porous matrix. Tablets manufactured by this technique have reported to usually disintegrate in 10-20 sec. Even solvents like cyclohexane; benzene can be used as pore forming agents.

The key to rapid disintegration for mouth dissolving tablets is the presence of a porous structure in the tablet matrix. Conventional compressed tablets that contain highly water-soluble ingredients often fall to dissolve rapidly because of low porosity of the matrix. Hence. To generate porous matrix, volatile ingredients are used that are later subjected to a process of sublimation.



Schematic Diagram of Sublimation Technique for Preparation of MDT



Direct Compression

It is the easiest way to manufacture tablets. Conventional equipment, commonly available excipients and a limited number of processing steps are involved in direct compression. Also high doses can be accommodated and final weight of tablet can easily exceed that of other production methods. 

Directly compressed tablet's disintegration and solubilization depends on single or combined action of disintegrates, water soluble excipients and effervescent agent. Disintegrate efficacy is strongly affected by tablet size and hardness. Large and hard tablets have disintegration time more than that usually required. As consequences, products with optimal disintegration properties often have medium to small size and /or high friability and low hardness. Breakage of tablet edges during handling and tablet rupture during the opening of blister alveolus, all result from insufficient physical resistance. 

Direct Compression technique can now be applied to preparation of ODT because of the availability of improved excipients especially superdisintegrants and sugar based excipients.  

 (a) Superdisintegrants:
In many orally disintegrating tablet technologies based on direct compression, the addition of superdisintegrants principally affects the rate of disintegration and hence the dissolution. To ensure a high disintegration rate, choice of suitable type and an optimal amount of disintegrant is important. Other formulation components such as water soluble excipients or effervescent agents can further enhance dissolution or disintegration properties. But main drawback of using effervescent excipients is their highly hygroscopic nature. 

 (b) Sugar Based Excipients:
This is another approach to manufacture ODT by direct compression. The use of sugar based excipients especially bulking agents like dextrose, fructose, isomalt, lactilol, maltilol, maltose, mannitol, sorbitol, starch hydrolysate, polydextrose and xylitol, which display high aqueous solubility and sweetness, and hence impart taste masking property and a pleasing mouthfeel. There are two types of sugar-based excipients on the basis of molding and dissolution rate.
  • Type 1 saccharides (lactose and mannitol) exhibit low mouldability but high dissolution rate.
  • Type 2 saccharides (maltose and maltilol) exhibit high mouldability and low dissolution rate.  
4.    Mass-Extrusion

This technology involves softening the active blend using the solvent mixture of water-soluble polyethylene glycol and methanol and subsequent expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablet. The dried cylinder can also be used to coat granules for bitter drugs and thereby achieve taste masking.

An important advantage of the hot melt extrusion method is that the drug/carrier mix is only subjected to an elevated temperature for about 1 min, which enables drugs that are somewhat thermo labile to be processed.

It is composed of   active ingredient and carrier, and prepare by hot-stage extrusion using a co-rotating twin-screw extruder. The concentration of drug in the dispersions is always 40% (w/w). The screw-configuration consist of two mixing zones and three transport zones distribute over the entire barrel length, the feeding rate is fix at 1 kg/h and the screw rate is set at 300 rpm. The five temperature zones are set at 100, 130, 170, 180, and 185C from feeder to die. The extrudates are collect after cooling at ambient temperature on a conveyer belt. Samples are milled for 1 min with a laboratory-cutting mill   and sieve to exclude particles >355┬Ám. 

Melt granulation

Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time consuming and uses less energy than wet granulation. It is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as griseofulvin. This approach to prepare FDT with sufficient mechanical integrity, involves the use of a hydrophilic waxy binder (Superpolystate©, PEG-6-stearate). Superpolystate© is a waxy material with a melting point of 33–37°C and a HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues.

Phase transition process

It is concluded that a combination of low and high melting point sugar alcohols, as well as a phase transition in the manufacturing process, are important for making FDTs without any special apparatus. FDT were produced by compressing powder containing erythritol (melting point: 122 °C) and xylitol (melting point: 93 95 °C), and then heating at about 93 °C for 15 min. After heating, the median pore size of the tablets was increased and tablet hardness was also increased. The increase of tablet hardness with heating and storage did not depend on the crystal state of the lower melting point sugar alcohol.

Cotton Candy Process

This process is so named as it utilizes a unique spinning mechanism to produce floss-like crystalline structure, which mimic cotton candy. Cotton candy process involves formation of matrix of polysaccharides or saccharides by simultaneous action of flash melting and spinning. The matrix formed is partially recrystallized to have improved flow properties and compressibility. The candy floss matrix is grinded and blended with drug and excipients and then compressed to ODT. This process is more helpful for high doses of drug and also increase mechanical strength of tablet. But high temperature process limits the use of this process.

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