Beyond compression: How powder properties affect tablet compression

Several factors affect tablet compression, such as compression machine design & settings, the powder formulation, and climatic conditions at the manufacturing site. Apart from compression physics and machine performance, compaction is strongly influenced by powder characteristics and machine parameters.

In general, a desirable powder blend must have good flow properties, compressibility, binding, and ability to form tablets. The hardness and friability must be within limits yet meeting the requirements of a drug release. Excellent quality of granules or a blend is one of the principal requirements for fabrication of good tablets. Let us take a look at these different properties of powder blends.

Moisture content

Moisture plays a significant role in all tablet manufacturing steps, and compression is no exception to this notion. Based on the study of moisture absorption, appropriate excipients such as disintegrants, direct-compression carriers, and binders can be selected to aid the compression. It also determines the required humidity and temperature, which are to be maintained during the manufacture of tablets. The moisture content, at a particular relative humidity (RH) and temperature, depends upon the chemical affinity, surface area, and available sites of interaction of the powder molecules. Moisture increases the tensile strength of the powder bed and decreases density variation, within a tablet thus, promoting interparticulate bond formation. In the presence of moisture, lower pressure is required for powder compaction.

For example, tablets in which Microcrystalline Cellulose (MCC) is used as one of the excipients, show increased hardness with increasing moisture content. On the other hand, lower moisture results in tablet lamination owing to increased yield force and elastic recovery.

Hydration/solvate state

The hydration state is important for crystalline powders. For these powders, the water of crystallization, in general, aids the formation of hard tablets by enabling good compression, and this is also true for tablets prepared using excipients of crystal hydrate nature, such as ferrous sulfate heptahydrate. In another study,[i] the effects of water present in the crystal lattices of p-hydroxybenzoic acid anhydrate (HA) and the monohydrate (HM) were studied. Both materials are structurally similar, in that, both the materials exhibit hydrogen-bonded zigzag-shaped layers that lie parallel to the plane. Upon compression, the zigzag-shaped layers of HA mechanically interlock, and this state prevents slip and reduces plasticity, whereas, in HM, the layers are separated because of the water molecules present in the crystals, thus facilitating slip and increasing plasticity. This situation increases the interparticulate bonding area when the same compaction pressure is applied. Furthermore, in the HM crystals, the water molecules form a 3-dimensional hydrogen-bonding network by increasing the lattice energy. As a result, HM compacts show greater tensile strength at zero porosity owing to increased bonding strength.

Crystal habit

Changes in crystal habit modulate the tableting property of drugs. For example, a study with tolbutamide showed that tolbutamide in its plate-like crystal form caused particle-bridging in the hopper of the tablet press and increased capping during tableting.[ii] Another study, involving L-lysine monohydrochloride dihydrate, showed that compared to the prism-shaped crystal habit, the plate-shaped habit improved tableting owing to the favorable orientation of the slip planes, thus increasing plasticity under load.[iii]

Surface properties

These properties of powders affect their flow and intermolecular attraction forces. Particles present on the surface of the powder contain atoms or ions that have an unequal distribution of intermolecular and intramolecular bonding forces as compared to those present within the powder. These unsatisfied attractive molecular forces extend over the small distance beyond the solid surface and result into free surface energy of solids. This free surface energy further limits the differential movement of particles when an external force is applied. Electrostatic forces, adsorbed moisture, and a residual solvent on the surface of solid particles are other types of resistance that prevent the relative movement of particles.

Surface characteristics of the powders are also affected by milling the particles before compaction. Particle pulverization results in a more disordered or amorphous surface of powders, and this characteristic may increase the deformability and enhance the tendency for forming interparticulate bonds, thereby facilitating compaction.


Porosity has been linked with one of the volume reduction mechanisms of powders. The porosity–pressure relation is one of the determinants of compressibility of powders. Measurement of a relative difference in porosity can yield information about the extent of elastic deformation of the powder bed during compression.

Flow properties

Powders with good flow properties are vital for proper die-filling during compression. Indirect compaction, this characteristic assumes particular importance. Many factors can adversely affect the flow of powders, such as excess moisture, lubricants, a high percentage of fines, and an electrostatic charge.

Particle size and particle size distribution

Average particle size is directly related to tablet tensile strength, and therefore, it is essential to select an appropriate particle size.

The effect of particle size on compaction has been studied for paracetamol. Two particle size fractions of paracetamol (<90 µm and 105–210 µm) produced weak tablets that exhibited capping. Besides, particles of 105–210-µm showed greater fragmentation than those of 90 µm. Further analysis revealed that a larger-size fraction of paracetamol produced denser compacts than did the smaller-size fraction, with low elastic recoveries and elastic energies.

Another study of paracetamol showed that particle size distribution does not affect tablet porosity and tensile strength during compression but has a significant influence on short-term post-compaction hardening.

Polymorphism and amorphism

Different polymorphic forms of drugs or excipients have a profound impact on compaction behavior. When different polymorphs of sulfamerazine—polymorph I and two batches of polymorph II of varying particle sizes [II(A) and II(B)]—were crystallized and compressed, significant differences were observed. Polymorph I exhibited superior tabletability and compressibility as compared to other polymorphic forms because of the presence of slip planes in the crystals of polymorph I but not in polymorph II. Owing to the slip planes, polymorph I had greater plasticity than polymorph II.[iv] A compression study of paracetamol revealed that the orthorhombic form has a better compression profile than the monoclinic form because of the presence of slip planes for crystal plasticity, increased fragmentation at low pressure, increased plastic deformation at higher pressure, and decreased elastic recovery, thus preventing the capping of tablets at high compression pressures.[v]

Amorphous materials, in general, tend to have better compaction properties because of the complete absence of long-range 3-dimensional intermolecular order and high plastic deformation. α-Cyclodextrin and spray-dried lactose fall into this category.

Salt form

Sun et al., in their study of L-lysine, highlighted the importance of the salt form of a drug for compaction.[vi] During the study, they analyzed the compaction behavior of a salt form of L-lysinium (a common cation) with different anions including acetate, monochloride, dichloride, L-aspartate, L-glutamate (dihydrate), and L-lysine (zwitterionic monohydrate) at various pressures. All the different salts showed different compaction behaviors. Also, the higher melting temperatures of the salts indicated high tensile strength at zero porosity because it implies strong intermolecular and interionic interactions in the crystals.



[i] Sun C, Grant DJ. Improved tableting properties of p-hydroxybenzoic acid by water of crystallization: a molecular insight. Pharm Res. 2004;21:382–6.
[ii] Li Destri G, Marrazzo A, Rescifina A, Punzo F. Crystal morphologies and polymorphs in tolbutamide microcrystalline powder. J Pharm Sci. 2013;102(1):73–83.
[iii] Sun C, Grant DJ. Influence of crystal shape on the tableting performance of L-lysine monohydrochloride dihydrate. J Pharm Sci. 2001;90:569–79.
[iv] Sun C, Grant DJW. Influence of crystal structure on the tableting properties of sulfamerazine polymorphs. Pharm Res. 2001;18:274.
[v] Joiris E, Di Martino P, Berneron C, Guyot-Hermann AM, Guyot JC. Compression behavior of orthorhombic paracetamol. Pharm Res. 1998;15:1122–30.
[vi] Sun C, Grant DJ. Compaction properties of L-lysine salts. Pharm Res. 2001;18(3):281–6.
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About Ajit Kanetkar

Mr. Ajit Kanetkar is an M. Pharm in 1982 from University Dept. of Pharmaceutical Sciences, Nagpur, India. He has 35 years of experience including 20 years in Pharma Mfg. in all dosage forms especially Sterile Products & Oral Solid Dosage forms. He has worked in pharma companies like Wockhardt, Cipla Group in India, and SM Pharma in Malaysia. He has been with ACG for almost 15 years, in which he was working extensively for over 8 years on introducing Fluid Bed Processing technology across India. He has now taken on the role of providing technical support to ACG group companies and coordinating technical seminars & training programs for customers in India and across the world.
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