Directly compressible adjuvant can be prepared by various methods, the outline and main features of the methods are depicted in Table11, 17, 18. Co-processing is the one of the most widely explored and commercially utilized method for the preparation of directly compressible adjutants. Hence, co-processing is discussed in more depth in the present review.

Methods used for development of co-processed Excipients
Following are the methods that can be used for manufacturing co-processed excipients. The most important features of various methods are depicted in Table 1.

Chemical Modification
Chemical modification is not preferred to a greater extent as it results in the formation of an altogether new chemical entity. One has to submit toxicological data for the new compound, which is quite cumbersome, time consuming, and relatively expensive e.g., ethyl cellulose, sodium carboxymethyl cellulose, methylcellulose, Hydroxypropyl methylcellulose from cellulose, and cyclodextrin from starch.'

Physical Modification
Physical modification is relatively simple and economical. The addition of impurities of similar structure to alter the crystal structure i.e. Dextrates or compressible sugar, i.e., Dicalcium phosphate, sorbitol.19 Researchers have also tried the simultaneous modification of both physical and chemical forms, e.g., pregelatinized starch or microcrystalline cellulose.'

Grinding and/or Sieving
The purpose of sieving or grinding materials for direct compression is primarily to control flow properties. The compressibility may also get altered because of changes in particle properties such as surface area and surface activation. Crystallized lactose monohydrate is either sieved or first ground and then sieved in order to make different sieve fractions available to the customers. Dicalcium phosphate dehydrate is commonly milled after crystallization for use in the wet granulation process. For direct compression, only the unmilled larger particles can be used, because they exhibit better flow and compaction properties.

Crystallization
Controlled crystallization would impart flowability to an excipient but not necessarily self-binding properties. The conditions of crystallization determine to a large extent the solid-state properties of directly compressible excipients. If polymorphism exists, the compactibility of the polymorphic forms may be quite different because of the internal arrangement of the molecules within the unit cells of crystals. Plastic deformation may occur depending on the dislocations and slip planes in the crystals. Crystalline substances are subject to such deformations depending on the symmetry within the crystal lattice. The crystal structure that has a greater degree of symmetry will be more prone to deformation on compression and compaction. (β-lactose monohydrate is obtained by crystallization at a temperature below 930 C while β-lactose is obtained by crystallization from a supersaturated solution at a temperature exceeding 93°C.

Spray Drying
Spray drying involves atomization of the aqueous solution or suspension into a spray. Contact between the spray and hot air in a drying chamber results in moisture evaporation and recovery of the dried product from the air. Because of the spherical nature of liquid particles after evaporation of water, the resulting spray dried material consist of porous spherical agglomerates of solid  particles that are fairly uniform size in the amorphous component generated by rapid cooling and crystallization act as a binder the atomization process drying chamber cooling rate of the solution, and rate of crystallization are the major factor that govern the shape and size of the spray- pharmaceutical excipient to successfully exemplify the spray drying technology. The other examples are depicted in Table 1.

Granulation /Aggiomeration
Granulation and agglomeration represent the transformation of small, cohesive, poorly flowable powders into a flowable and directly compressible from. Granulation results in nearly spherical particles with relatively high bulk density and strength. Agglomeration on the other hand, leads to irregularly shaped porous particles with relatively low bulk density and strength. When the primary panicles have binding properties of their own, the addition of binder is not necessary. 

Limitation of co-proceeded excipients
A co-proceeded adjuvant lacks official acceptance in the pharmacopeia. For this reason, a combination filler binder will not be accepted by the pharmaceutical industry until it exhibits significant advantages in tablet compaction when compaired to the physical mixture of the Excipients. Exceptions are spread dried dextrose maltose and compressible sugar that although being co-processed product are official in USP/NF. The ratio of the excipients in a mixture is fixed and in developing a new formation. A fixed ratio of the excipient may not be an optimum choice for the API and the dose per tablet under development.

Table 3. Methods used for manufacturing of directly compressible excipients11,17,18.
METOD	ADVATAGES & LIMITATIONS	EXAMPLE
Chemical modification	Relative expensive, Time consuming, Require toxicological data	Ethyl cellulose, Methyl cellulose, Hydroxyl propyl methyl cellulose, Na-CMC, Cyclodextrin.
Physical modification	Relatively simple & economical	Dextrates or compressible sugars, sorbitol.
Grinding &/or Sieving	Compressibility may alter because of Change in partical properties such as Surface area.	α-lactose monohydrate(100#), Dibasiccalciumphosphate.
Crystallization	Impart flowability to excipients but not necessarily self-binding properties.	Β-lactose, Dipac.
Spray Drying	Spherical shape & uniform size gives spray dried materials, good flowability & poor workability.	Spray dried lactose, Emdex, fast flow lactose, Avicle PH, Karion instant, TRI-CAFOS S, Advantose 100.
Granulation	Transformation of small, cohesive & poorly flowable powders.	Granulated lacitol Tabletose.
Dehydration	Increased binding properties by thermal & chemical dehydration.	Anhydrous α-lactose