However, the vast majority of drugs are not able to spontaneously fill the matrix of the tablet machine due to a significant (more than 70%) content of fine fractions and irregularities in the surface of the particles, causing strong inter-particle friction. In these cases, auxiliary agents that improve the flow properties and belong to the class of sliding agents are added. Tablets of vitamins, alkaloids, acetylsalicylic acid, phenobarbital, ascorbic acid, sodium hydrocarbonate, streptocide, and phenacetin are prepared in this way. The mentioned characteristics are very important for the control of substances used in the technology of direct pressing, especially g large quantities, because the quality of tablets in this case will directly depend on the technological parameters of the tablet mass, its friability, pressability and compactability. It is experimentally established that the lower the concentration in the tablet mass of a component, the finer its particles should be. tHe can get a homogeneous tablet mass consisting of components with sharply different particle sizes. It is known that a system consisting of two fine powders forms more homogeneous and stable mixtures than a system in which the particles of one component are larger than the other. To obtain the optimal composition of the mixture of multicomponent drugs, it is desirable to observe the following conditions: the particle sizes of individual components should correspond to their concentration, the density of substances of individual components is desirable to select close to each other, the shape of the particles should be close to spherical. If the medicinal substance is suitable for the direct pressing process, it is tabletized using the usual excipients. If the drug substance is not suitable for direct pressing when using conventional excipients, excipients with sufficient binding effect on the particles are used, or granules of the drug substance with a binder suitable for direct pressing are used. Currently, tabletting without granulation (direct pressing) is carried out by the following methods: with the addition of excipients that improve the technological properties of the material; by forced feeding of the tabletting material from the feed hopper of the tabletting machine into the matrix; pre-directed crystallization of the pressed substance.

Pre-directed crystallization is one of the most complex methods of obtaining drug substances suitable for pressing, which consists in achieving the tabletable substance in crystals of a given bulkiness, pressability and humidity by selecting certain crystallization conditions. The result is a crystalline drug substance with crystals of isodiametric shape, freely pouring out of the funnel and therefore easily subjected to volumetric dosing, which is a prerequisite for direct pressing. This method is used to obtain tablets of acetylsalicylic and ascorbic acid. To increase the compressibility of drug at direct pressing in the composition of the powder mixture add dry binders – most often microcrystalline cellulose (MCC) or polyethylene oxide (PEO). Due to its ability to absorb water and hydrate individual layers of tablets, MCC has a favorable effect on the process of drug release. With MCC, strong but not always well disintegrating tablets can be manufactured. It is recommended to add ulypra-amylopectin together with MCC to improve tablet disintegration. Copovidone (vinylpyrrolidone copolymer) has a small particle size, which results in improved plasticity and excellent dry binding capacity. The analysis of the presented binders shows that Collidon VA 64 fine has one of the best binding effects when tablets are obtained by direct pressing. In direct pressing it is recommended to use modified starches as binders, which enter into chemical interaction with drug substances, significantly affecting their release and biological activity. Often used milk sugar as a means of improving the bulkiness of powders, as well as granulated calcium sulfate, which has good bulkiness and provides the receipt of tablets with sufficient mechanical strength. Cyclodextrin is also used, which increases the mechanical strength of tablets and their disintegration.
In direct pressing, maltose is recommended as a substance that provides a uniform filling rate and has negligible hygroscopicity. A mixture of lactose and cross-linked polyvinylpyrrolidone is also used. Anhydrous lactose is capable of direct pressing and has good friability. It does not lose its tabletability properties even when ground to a fine powder, although its flowability is reduced. Spray-dried lactose consists of microcrystals – particles of amorphous and vitreous structure.