How powder properties affect tablet compression

Several factors affect tablet compression, such as compression machine design and settings, formulation, and plant climate conditions. Apart from the compression physics and machine performance, compaction is largely influenced by powder characteristics and machine parameters.

In general, a desirable powder blend must have good flow properties, compressibility, binding, ability to form tablets of good hardness, and friability within limits yet meeting requirements of drug release. Quality of granules or blend is one of the principal requirement to make good tablets. Let us have 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. 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 manufacturing of tablets. The moisture content, at a particular 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 presence of moisture, lower pressure is required for powder compaction.

For example, tablets, in which MCC was used as one of the excipients, showed increased hardness with increasing moisture content. On the other hand, lower moisture resulted in tablet lamination owing to increased yield force and elastic recovery.

Hydration/solvate state

Hydration state is important for crystalline powders. For these powders, water of crystallization in general aids in formation of strong tablets by enabling well compression and it is further proven by compression of ingredients of crystal hydrate nature, such as ferrous sulfate heptahydrate. In another study,[i] effect of the water present in the crystal lattices of p-hydroxybenzoic acid anhydrate (HA) and the monohydrate (HM) were studied. Both the 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 which inhibits slip and reduces plasticity, whereas in HM, the layers are separated because of the water molecules present in the crystals allowing easier slip and greater plasticity. This 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 of this, 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, tolbutamide in its plate-like crystal form caused particle-bridging in the hopper of the tablet press and increased capping problem during tableting. [ii] Another study involving L-lysine monohydrochloride dihydrate showed that compared to prism-shaped crystal habits, plate-shaped one improved tableting via favourable orientation of the slip planes thus, increasing plasticity under load. [iii]

Surface properties

Surface properties of powders affect their flow and intermolecular attraction forces. Particles present on the surface of the powder contain atoms or ions which have an unequal distribution of intermolecular and intramolecular bonding forces compared to those present within a particle. 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 residual solvent on the surface of solid particles are other types of resistance which prevent the relative movement of particles.

Surface characteristics of the powders are also affected by milling of the particles prior to compaction. Particle pulverization results in more disordered or amorphous surface of powders which may increase the deformability and enhance the tendency of forming interparticulate bonds thus facilitating compaction.[iv]

Porosity

Porosity has been linked with one of the volume reduction mechanism of powders. Porosity-pressure relationship is one of the determinant of compressibility of powders. Measurement of relative difference in porosity can give the 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. In direct compaction, it assumes a special importance. There are many factors which can affect the flow of powders adversely, such as excess moisture, lubricants, high percentage of fines, and electrostatic charge.

Particle size/Particle size distribution

An average particle size is directly related to the tablet tensile strength, and therefore, it is important to select an appropriate particle size for powders.

The effect of particle size on compaction was studied for paracetamol. Two particle size fractions of paracetamol (<90 µ and 105–210 µ) produced very weak tablets with capping. Also, in comparison with 90 µ particles, 105-210 µ particles showed more fragmentation. Further analysis revealed that larger size fraction of paracetamol produced denser compacts than the smaller fraction, with low elastic recoveries and elastic energies.

Another study of paracetamol showed that the particle size distribution had not affected tablet porosity and tensile strength during compression but had a significant effect on the short-term post-compaction hardening.

Polymorphism/Amorphism

Different polymorphic forms of drugs/excipients have profound impact on compaction behavior. When different polymorphs of sulfamerazine – polymorph I and two batches of polymorph II of different particle size [II(A) and II(B)] were crystallized and compressed, significant differences were found. Polymorph I exhibited superior tabletability and compressibility compared to other polymorphic forms because of the presence of slip planes in the crystals of polymorph I but not in II. The slip planes provided greater plasticity compared to polymorph II, enhancing tabletability and compressibility of polymorph I. [v] The compression study of paracetamol revealed that between the pure orthorhombic and monoclinic polymorphs, the orthorhombic form exhibited better compression profile because of the presence of sliding planes for crystal plasticity, greater fragmentation at low pressure, increased plastic deformation at higher pressure, and lower elastic recovery, thus eliminating capping of tablets at high compression pressures. [vi]

Amorphous materials, in general, tend to show better compaction properties because of the complete absence of long-range, 3-dimensional, intermolecular order, and higher plastic deformation. α-cyclodextrin and spray-dried lactose come under this category.

Salt form

Sun et al, through their study of L-lysine, highlighted the importance of salt form of drug in compaction. [vii] During the study, they analysed the compaction behavior of 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 different salts showed different compaction behavior. In addition, the higher melting temperatures of the salts indicated high tensile strength at zero porosity, as it implied strong intermolecular and interionic interactions in the crystals.

 

 

References

[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 Jan;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] Tablet mechanical strength
[v] Sun C, Grant D.J.W. Influence of crystal structure on the tableting properties of sulfamerazine polymorphs.  Pharm Res. 2001;18: 274.
[vi] Joiris E, Di Martino P, Berneron C, Guyot-Hermann AM, Guyot JC. Compression behavior of orthorhombic paracetamol. Pharm Res. 1998;15:1122–30.
[vii] Sun C, Grant DJ. Compaction properties of L-lysine salts. Pharm Res. 2001 Mar;18(3):281-6.

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