Anil Kumar Sahdev*, Somya Purwar
GNIT College of Pharmacy Greater Noida UP India
Tablet is a unit solid dosage form, due to high precision dosing, manufacturing efficiency and patient compliance make tablet to most popular dosage forms. Compression (lessening in the bulk volume of material as a result of deracination of gaseous phase) and compaction (alteration of powder into coherent specimen) are the duet constitutive parts of tablet manufacturing. In this review discuss various types of excipients and their properties, including steps and mechanism of tablet compaction. Mechanistic aspects of tableting can be studied using several theories like mechanical theory, intermolecular theory, and liquid surface film theory. These all parameters have potential importance in various pharmaceutical research and development. Also, the mathematical equation used to characterize compaction and compression events. Compaction related physic-technical properties of commonly used tableting excipients have been reviewed with emphasis on selecting pleasantly combination to attenuate tableting problems. Specialized tools like co-processing of API and excipients properties like particle size and shape, surface area, density, strength and friability used to amend compression of tableting.
The oral route of drug administration is the most convenient method of drug administration for systemic effects. It is mostly used for the neutral drugs. It may be in the form of tablets, capsules, syrups, emulsions, powders. Tablets and capsules act for unit dosage forms in which one usual dose of the drugs has been accurately placed. Pharmaceutical product have been administered to the body using drugs and suitable excipients, for rapid and systemic absorption of drugs1,2.
Accepted on 11.10.2018 © A&V Publications All right reserved
Of the two oral solid dosages forms commonly employed in this country, the tablet and the capsule, the tablet has a number of advantages. One of the major advantages of the tablet over capsule, which has recently proved significant, is that the tablet is an essentially tamperproof dosage form3.
Tablets are made by compressing a drug or drugs with excipients on stamping machines called presses. Tablets presses are either single-punch or multi station rotary presses.
Fig.1 Excipients used in Tablet compression
Compaction: compaction of a powder is a general term used to describe a situation in which powdered material is subjected to some level of mechanical force.
Compression: compression of a powder means reduction in the bulk volume of a material as a result of displacement of the gaseous phase under pressure.
Fig.2 General steps in tablet manufacturing
The complete cycle of tablet compaction occurs in four steps-
Stage 1- Top punch is withdrawn from the die by the upper cam. Bottom punch is low in the die so powder falls in through the hole and fills the die.
Stage 2 –Bottom punch moves up to adjust the powder weight. It raises and expels the excess powder.
Stage 3 –Top punch is driven into the die by upper cam and bottom punch is lowered by lower cam. Both punches heads pass between heavy rollers to compress the powder.
Stage 4 – Top punch is withdrawn by the upper cam. Lower punch is pushed up and expels the tablet. Tablet is removed from the die surface by surface plate.
Fig.3 Steps involved in tablet compaction
Manufacture of Granulations:
The manufacture of granulations for tablet compression may follow one or a combination of 3 methods8.
is a popular choice because it provide the shortest, most effective and least complex wat to produce tablets. The manufacture can blend an API with the excipient and lubricant, followed by compression, no additional processing steps are required. There are a few crystalline substances such as sodium chloride, sodium bromide and potassium chloride that may be compressed directly. Direct compression materials, in addition to possessing good flow and compressibility, must be inert, tasteless, rework able, able to disintegrate and inexpensive9,10.
has been used for many years, and is valuable technique in situations where the effective dose of a drug is too high for direct compaction, and the drug is sensitive to heat, moisture, or both. Many aspirin and vitamin formulations are prepared for tableting by compression granulation. Compression granulation involves the compaction of the components of a tablet formulation by means of a tablet press or specially designed machinery, followed by milling and screening, prior to final compression into a tablet. When a initial blend of powder if forced into a dies of a large capacity tablet press and is compacted by means of flat-faced punches, the compacted masses are called slugs, and the process is referred to as “slugging”. The slugs are then screened or milled to produce a granular form of tabletting material11-13.
processes involve the wet massing of the powders, wet sizing or milling and drying. Wet granulation forms the granules by binding the powders together with an adhesive, instead of by compaction14, 15.
There are many formulation and process variables involved in the granulation step, and all of these can affect the characteristics of the granulations.
1. Particle size and shape:
The particle size of a granulation is known to affect the average tablet weight variation, disintegration time, granule friability, flow ability and drying rate of granules16. The exact effect of granule size and size distribution on processing requirements, bulk granulation characteristics and final characteristics of tablet depends upon the formulation ingredients and their concentrations, as well as the type of granulating equipment and processing conditions17,18.
2. Surface area:
The determination of the surface area of finely milled drug powder may be of value for drugs that have only limited water solubility. Particle size and surface area of the drug, can have a significant effect upon dissolution rate19.
Density of granule may influence compressibility, tablet porosity, dissolution and disintegration rate. Dense, hard granules may require higher compressible loads to produce a cohesive compact20. The higher compression load, has the potential of increasing the tablet disintegration and drug dissolution time.
Density is calculated from the volume of intrusion fluid displaced in the pycnometer by a given mass of granulation21.
D=M / Vp - Vi
Vp= total volume of pycnometer,
Vi= volume of intrusion fluid
The equation of bulk density (ρb) is –
ρb = M / Vb
M = mass of particles,
Vb = total volume of packing
4. Strength and Friability:
A granule is an aggregation of component particles that is held together by bond strength. The strength of a wet granule is due to the surface tension and capillary forces. Upon drying, the granule has strong bond due to fusion or recrystallization of particles. The resultant strength of a granules depends on base material, the kind and amount of granulating agent used, the granulating equipment used22-24.
5. Flow properties:
The flow property of a material result from many forces. Solid particles attract to each other, and forces acting between particles when they are in contact. There are many forces that can act between solid particles; surface tension force, frictional force, mechanical force, electrostatic force, cohesive or van der waals forces. These forces can also effect granule properties such as particle size, particle size distribution, particle shape, surface texture, roughness and surface area25,28.
Angle of repose is commonly used for the measurement of flow properties of powder and granules.
Θ = tan -1(h/r)
Θ = is angle of repose,
h = height of heap, r = radius of heap
Table 1. Angle of repose
Angle of repose
Very very poor
The process of consolidating and compaction of powder or granule material to form a tablet is complex. The basic tool that has been developed for studying the compression process is the instrumented tablet press29.
Physics of tablet compaction:
Fig.4 mechanism of tablet compaction
1. Repacking or rearrangement of particles:
The nonisostatic compression of powder or granular material to produce a compact is a complex process, arising from the numerous internal processes that lead to consolidation. When a powder is compressed initially the particles are rearranged under low compaction pressures to form a closer packing structure30,31. The finer particles enter the voids between the larger ones and give a closer packing arrangement. In this process, the energy is evolved, as a result of inter particulate friction and there is an increase in the amount of particle surface area capable of forming inter particulate bonds32. As the pressure increases, further rearrangement is prevented and subsequent volume reduction is accomplished by plastic and elastic deformation and/or fragmentation of the particles33.
The type of deformation depends not only on the physical properties of the material but also on the rate and magnitude of the applied force and the duration of locally induced stress34.
As the upper punch penetrates the die containing the powder bed, initially there are essentially only points of contact between the particles35. The application of the external forces to the bed results in force being transmitted in through these interparticulate points of contact, leading to development of stress and local deformation of the particles. Energy is lost at this stage as a result of interparticulate and the die-wall friction, as well as deformation. Although, under the influence of an applied pressure, the particles not only deform plastically or elastically, but also fragment to form smaller particles (termed as brittle fracture)36,37. The deformation is reversible and the particles inside the powder bed regain their original shapes.
Fig.5 Mechanism of deformation
As compression force increases deformed particles start fragmentation due to high load, particles breaks into smaller fragments leading to formation of new bonding areas. The fragment undergo densification with infiltration of small fragments into voids.
Some particles undergo structural break down called as brittle fracture38.
4. Bonding of particles:
The mechanical strength of a tablet depends on the dominating bonding mechanism between the particles and the surface area over which these bonds act.33 When the surfaces of two particles approach each other closely enough, their surface energies result in a strong attractive force, a process called cold welding39. This hypothesis is favoured as a major reason for the increasing mechanical strength of a powder bed when subjected to compression force. Most particles have an irregular shape, so that there are many points of contact in the bed of powder. As the force is applied to the powder bed, this transmission may result in generation of considerable frictional heat. If this heat is not lost, the local rise in temperature could be sufficient to cause melting of contact area of the particles, which would relieve the stress in that particular region. In that case, the melt solidifies giving rise to fusion bonding40,41,42.
Bonding of particles governed by several theories-
A) The mechanical theory-:
Mechanics of a material deals with the behaviour of a solid body subjected to various types of loading. It occurs between irregular shaped bodies. Mechanical interlocking may increases the contact points between particles. The mechanical theory proposes that under pressure the individual particles undergo elastic/plastic or and brittle deformation and that the edges of the particles intermesh deforming a mechanical bond.
· If only the mechanical bond exists, the total energy of compression is equal to the sum of the energy of deformation, heat and energy absorb for each constituent.
· Mechanical interlocking is not a major mechanism of bonding in pharmaceutical tablet42.
B) Intermolecular theory- Intermolecular forces:
are the forces which mediate interaction between , including forces of attraction or repulsion which act between molecules and other types of neighbouring particles. e.g., or . • The molecules [or ions] at the surface of solid have unsatisfied forces [surface free energy] which interact with the other particles in true contact43,44.
Under pressure the molecules in true contact between new clean surfaces of the granules are close enough so that vender-walls forces interact to consolidate the particles.
Materials containing plenty OH groups may also create hydrogen bonds between molecules.
C) Liquid surface film theory-
This theory attributes bonding to the presence of a thin liquid film which may be the consequences of fusion or solution at the surface of the particles. This theory is a combination of Solid bridge, Hot welding and Cold welding theory45.
5. Deformation of solid body:
As the applied force /pressure is further increased the bonded solid is consolidated towards a limiting density by plastic/ elastic deformation of the tablet within the die46.
The last stage in compression cycle is ejection from die. Ejection phase also requires force to break the adhesion between die wall and compact surface and other forces needed to complete ejection of tablet. The force necessary to eject a tablet involves the distinctive peak force required to initiate ejection, by breaking of die wall–tablet adhesion. The second stage involves the force required to push the tablet up the die wall, and the last force is required for ejection. Variations in this process are sometimes found when lubrication is inadequate and a slip-stick condition occurs between the tablets and dies wall, with continuing formation and breakage of tablet die–wall adhesion47,48.
Force distribution during compaction:
FA = FL + FD
FA- force applied to upper punch, FD- force transmitted to lower punch, FD- reaction at die wall
Mean compaction force-
FM = (FA + FL) /2
Compaction equation –
1) Heckel equation-:
The Heckel equation is based on the assumption that densification of the bulk powder under force follows first-order kinetics The Heckel equation is expressed as;
In [1/1-D] = KP +A
Where, D is the relative density of the tablet (the ratio of tablet density to true density of powder) at applied pressure P, and K is the slope of straight line portion of the Heckel plot49.
THE SIGNIFICANCE OF HECKEL PLOT50:
1. The Heckel constant k has been related to the reciprocal of the mean yield pressure, which is the minimum pressure required to cause deformation of the material under compression.
2. The intercept of the curve portion of the curve at low pressure represents a value due to densification by particle rearrangement.
3. The intercept Obtained from the slop of the upper portion of the curve is a reflection of the densification after consolidation.
4. A large value of the Heckel constant indicates the onset of plastic deformation at relatively low pressure.
5. A Heckel plot permits an interpretation of the mechanism of bonding.
Fig.6 Heckel plots – For plastic deforming bodies
Fig. 7 For fragmenting materials
Weakness of hackle plots51:
Shape of the plot os very sensitive for small errorsin the determination of powder true density.
Linear part of plot is sometime difficult to determine.
This plot determination need very accurate data.
The basis for Kawakita equation for powder compression is that the particles are subjected to compressive load in equilibrium at all stages of compression, so that the product of pressure term and volume term is constant.
Pa/C = 1/ab +Pa/a
C= V0 -V /V0
Where, Pa is the applied axial pressure, a is the degree of volume reduction for the bed of particles, and b is a constant that is inversely related to the yield strength of particles. C is the degree of volume reduction, V is volume of compact at pressure, and V0 is the initial apparent volume of powder. This equation holds best for soft fluffy pharmaceutical powders, and is best used for low pressures and high porosity situations52-54.
The Walker equation is based on the assumption that the rate of change of pressure with respect to volume is proportional to the pressure, thus giving a differential equation
Log P = -L × V’/V0 +C1
Where, V0 is the volume at zero porosity. The relative volume is V′/V0 = V = 1/D, C1 is constant. The coefficient L is referred to as the pressing modulus 55,56.
Compaction and compression are an integral processes for the manufacture of tablets, and it is pertinent to understand the underlying physics of compaction. Complete understanding of compaction physics still eludes us, many variables such as inherent deformation behaviour of drugs/excipients, solid-state properties, and process parameters are known to affect the final attributes of tablets. A due consideration to the variables of compaction process, can aid a pharmaceutical scientist to design optimum formulation devoid of problems such as capping, lamination, picking, and sticking. Various granulating steps, surface area, particle size and shape, strength and friability, density and flow properties can help in deciphering the dynamics of the process. Optimization of excipient, granulation and compaction forces and equations can help in achieving satisfactory tensile strength and desired biopharmaceutical properties in tablet drug products.
1. Banker GS, Anderson NR., “Tablets”, In: Lachman L, Liberman HA, Kanig JL, editors "The Theory and Practice of Industrial Pharmacy", 3rd ed., Bombay, Varghese Publishing; 1976.
2. Jeffrey L, Czeisier, Karl PP. Diluents. In: James CB, James S, editors. Encyclopedia of Pharmaceutical Technology. New York: Marcel Dekker; 1991.
3. Guo HX, "Compression behavior and enteric film coating properties of cellulose esters [dissertation]", Finland, University of Helsinki; 2002.
4. Jivraj M, Martini LG, Thomson CM. "An overview of the different excipients useful for the direct compression of tablets", Pharm Sci Tech Today. 2000; 3: 58–63.
5. Gohel MC, Jogani PD. “A review of co-processed directly compressible excipients", J. Pharm Sci. 2005; 8: 76–93.
6. Marshall K. “Compression and consolidation of powdered solids”, In: Lachman L, Lieberman HA, Kanig JL, editors, “The Theory and Practice of Industrial Pharmacy", 3rd ed. Bombay, Varghese Publishing; 1987.
7. Moreton RC. Tablet excipients to the year 2001: A look into the crystal ball. Drug Dev Ind Pharm. 1996; 22:11–23.
8. Leuenberger H, Leu R, "Formation of a tablet: a site and bond percolation phenomenon", J Pharm Sci. 1992;81:976–82.
9. Joiris E, Di Martino P, Berneron C, Guyot-Hermann AM, Guyot JC, "Compression behavior of orthorhombic paracetamol" Pharm Res. 1998;15:1122–30.
10. Arambulo, A.S., Fu, H.S., Deardorff, D.L. Compressed tablets; weight variation. J Am Pharm Assoc Am Pharm Assoc. 1953; 42:692–694.
11. Tang, E.S.K., Chan, L.W., Heng, P.W.S. Coating of multiparticulates for sustained release. Am J Drug Deliv. 2005; 3:17–28.
12. Mitra, B., Chang, J., Wu, S.J. et al, Feasibility of mini-tablets as a flexible drug delivery tool. Int J Pharm. 2017; 525:149–159.
13. Reimerdes D, Aufmuth KP. Tabletting with Co-processed Lactose-Cellulose Excipients. Manuf Chem. 1992; 63:21–4.
14. Goto, K., Sunada, H., Danjo, K., Yonezawa, Y. Pharmaceutical evaluation of multipurpose excipients for direct compressed tablet manufacture: comparisons of the capabilities of multipurpose excipients with those in general use. Drug Dev Ind Pharm. 1999; 25:869–878.
15. Yeleken, G., Kotłowska, H., Sznitowska, M., Golenia, E., Ustenova, G. Development of direct compressed loratadine minitablets. J Pharm Sci Res. 2017; 9:401–406.
16. Roberts, M., Vellucci, D., Mostafa, S., Miolane, C., Marchaud, D. Development and evaluation of sustained-release Compritol® 888 ATO matrix mini-tablets. Drug Dev Ind Pharm. 2012; 38:1068–1076
17. S. S. Biradar, S. T. Bhagavati, and I. J. Kuppasad, “Fast dissolving drug delivery systems: a brief overview,” The Internet Journal of Pharmacology, vol. 4, no. 2, 2006.
18. York, P. "Crystal engineering and particle design for the powder compaction process", Drug Dev Ind Pharm. 1992; 18: 677–721.
19. Adam A, Schrimpl L, Schmidt PC, "Factors influencing capping and cracking of mefenamic acid tablets" Drug Dev Ind Pharm. 2000; 26: 489–97.
20. Kogawa AC, Salgadoa HRN (2016) Optimization of Microbiological Method by Turbidimetry for Quantification of Rifaximin Tablets: Validation, Application and Evaluation of Degraded Compounds. Pharm Anal Acta 7: 518.
21. Di Martino P, Scoppa M, Joiris E, Palmieri GF, Andres C, Pourcelot Y, Martelli S, "The spray drying of acetazolamide as method to modify crystal properties and to improve compression behavior", Int J Pharm. 2001;213:209–21
22. S. Vidyadhara, J. R. Babu, R. Sasidhar et al., “Formulation and evaluation of glimepiride solid dispersions and their tablet formulations for enhanced bioavailability,” Pharmanest, vol. 2, no. 1, pp. 15–20, 2011.
23. Gohel MC, Jogani PD, "Exploration of melt granulation technique for the development of coprocessed directly compressible adjuvant containing lactose and microcrystalline cellulose" Pharm Dev Technol. 2003;8:175–85.
24. Newton AMJ, Bindu B, Archana C (2016) Comparative Study on Starch Citrate Vs Other Super Disintegrants in the Formulation Characteristics and In vitro Profile of Ondansetron Sublingual Tablets by Direct Compression. Journal of Pharmacy and Pharmaceutical Sciences.
25. Srivastava R, Chaturvedi D (2015) Formulation, Characterization and Evaluation of Gastro-Retentive Floating Tablets of Norfloxacin. Research and Reviews in Pharmacy and Pharmaceutical Sciences.
26. Pontier C, Viana M, Champion E, Bernache-Assollant D, Chulia D, "About the use of stoichiometric hydroxyapatite in compression-incidence of manufacturing process on compressibility", Eur J Pharm Biopharm. 2001; 51: 249–57.
27. Akande OF, Ford JL, Rowe PH, Rubinstein MH, "The effects of lag-time and dwell-time on the compaction properties of 1:1 paracetamol/microcrystalline cellulose tablets prepared by pre-compression and main compression", J Pharm Pharmacol. 1998; 50: 19–28.
28. Sindhu.P (2014) Formulation Development and Evaluation of Bi-Layer Sustained Release Tablets of Amlodipine and Metaprolol. Journal of Pharmacy and Pharmaceutical Sciences.
29. Rani TS, Sujatha K, Chitra K, Jacob DM, Yandapalli R, et al. (2012) Spectrophotometric Method for Estimation of Tenofovir Disoproxil Fumarate in Tablets. Pharmaceutical Analysis.
30. Raja M, Geetha G, Sangaranarayanan A (2012) Simultaneous, Stability Indicating Method Development and Validation for Related Compounds of Ibuprofen and Paracetamol Tablets by RP-HPLC Method. J Chromat Separation Techniq.
31. Khattak S, Malik F, Hameed A, Ahmad S, Rizwan M, et al. (2010) Comparative Bioavailability Assessment of Newly Developed Flurbiprofen Matrix Tablets and Froben SR® Tablets in Healthy Pakistani Volunteers. JBB 2: 139-144
32. Sonnergaard JM. "A critical evaluation of the Heckel equation", Int J Pharm. 1999; 193: 63–71.
33. Davies P. “Oral solid dosage forms" In: Gibson M, editor. “Pharmaceutical Preformulation and Formulation", Colorado, Interpharm; 2001.
34. Prasanth VV, Lohumi A, Tribedi S, Mathappan R, Mathew ST, et al. (2013) Formulation and Evaluation of Gastro Retentive Floating Tablets of Stavudine. Journal of Pharmacy and Pharmaceutical Sciences.
35. Celik M. “Compaction of multiparticulate oral dosage forms", In: Ghebre-Sellassie I, editor “Multiparticulate Oral Drug Delivery", New York, Marcel Dekker; 1994.
36. Muñoz E, Horacio D, Espinal E and Yépes N (2014) Bioequivalence Study of Two 10 mg Montelukast Immediate-Release Tablets Formulations: A Randomized, Single-Dose, Open-Label, Two Periods, Crossover Study. J Bioequiv Availab.
37. Hiestand EN, Wells JE, Peot CB, Ochs JF. "Physical processes of tableting", J Pharm Sci. 1977; 66: 510–9.
38. Garekani HA, Ford JL, Rubinstein MH, Rajabi-Siahboomi AR. "Effect of compression force, compression speed, and particle size on the compression properties of paracetamol", Drug Dev Ind Pharm. 2001; 27: 935–42.
39. Rees JE, Rue PJ. "Time-dependent deformation of some direct compression excipients", J Pharm Pharmacol. 1978; 30: 601–7.
40. Danielson DW, Morehead WT, Rippie EG. "Unloading and postcompression viscoelastic stress versus strain behavior of pharmaceutical solids", J Pharm Sci. 1983; 72: 342–5.
41. Konkel P, Mielck JB. "Associations of parameters characterizing the time course of the tableting process on a reciprocating and on a rotary tableting machine for high-speed production", Eur J Pharm Biopharm. 1998; 45: 137–48.
42. Antikainen O, Yliruusi J. "Determining the compression behavior of pharmaceutical powders from the force-distance compression profile", Int J Pharm. 2003; 252: 253– 61.
43. Holzer AW, Sjorgen J. "Friction coefficient of tablet masses", Int J Pharm. 1981; 7: 269–77.
44. Kawakita K, Hattori I, Kishigami M. "Characteristic constants in Kawakita's powder compression equation", J Powder Bulk Solid Technology. 1977; 1:3–8.
45. Prasanth VV, Sarkar S, Tribedi S, Mathappan R, Mathew ST, et al. (2013) Formulation and Evaluation of Orodispersible Tablets of Salbutamol Sulphate. Journal of Pharmacy and Pharmaceutical Sciences.
46. Khattak S, Malik F, Hameed A, Ahmad S, Rizwan M, et al. (2010) Comparative Bioavailability Assessment of Newly Developed Flurbiprofen Matrix Tablets and Froben SR® Tablets in Healthy Pakistani Volunteers. JBB 2: 139-144.
47. Walker EE. "The properties of powder-Part VI-The compressibility of powders", Trans Faraday. 1923; 19: 73–82.
48. Tye CK, Sun CC, Amidon GE. "Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction", J Pharm Sci. 2005; 94: 465–72.
49. Garekani HA, Ford JL, Rubinstein MH, Rajabi-Siahboomi AR. "Effect of compression force, compression speed, and particle size on the compression properties of paracetamol", Drug Dev Ind Pharm. 2001; 27: 935–42.
50. Trevor MJ, Ho AYK, Barker MJ. The use of instrumentation in tablet research, devlopment and production. Pharm Technol. 1985;42–8.
51. Denny PJ. Compaction equations: a compression of the Heckel and Kawakita equations. Powder Technol. 2002; 127:162–72.
52. Jonat S, Hasenzahl S, Gray A, Schmidt PC. Mechanism of glidants: investigation of the effect of different colloidal silicon dioxide types on powder flow by atomic force and scanning electron microscopy. J Pharm Sci. 2004; 93:2635–44.
53. Kawashima Y, Imai M, Takeuchi H, Yamamoto H, Kamiya K, Hino T. Improved flowability and compactibility of spherically agglomerated crystals of ascorbic acid for direct tabletting designed by spherical crystallization process. Powder Technol. 2003; 130:283–9.
54. Podczeck F, Newton JM. Calculation of the brittle fracture tendency (BFP) of tablets. Int J Pharm. 2005; 294:269–70.
55. Amin MC, Fell JT. Comparison studies on the percolation thresholds of binary mixture tablets containing excipients of plastic/brittle and plastic/plastic deformation properties. Drug Dev Ind Pharm. 2004; 30:937–45.
56. Rao KP, Chawla G, Kaushal AM, Bansal AK. Impact of solid-state properties on lubrication efficacy of magnesium stearate. Pharm Dev Technol. 2005; 10:423–37.
57. Mohan Shailender, compression physics of pharmaceutical powders: a review. IJPSR, 2012; Vol. 3(6): 1580-1592.
Accepted on 25.10.2018 © A&V Publications All right reserved