Compact and Compression : Compact and Compression By Chetana Modi Advantages of tablets : Advantages of tablets Production aspect
Large scale production at lowest cost
Easiest and cheapest to package and ship
User aspect (doctor, pharmacist, patient)
Easy to handling
Lightest and most compact
Greatest dose precision & least content variability
Coating can mark unpleasant tastes & improve pt. acceptability Disadvantages of tablets : Disadvantages of tablets Some drugs resist compression into dense compacts
Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability
Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating. Ingredients used in tablets : Ingredients used in tablets Drugs
Fillers, diluent, bulking agent
To make a reasonably sized tablet
To bind powders together in the wet granulation process
To bind granule together during compression
To promote breakup of the tablets
To promote rapid release of the drug
To reduce the friction during tablet ejection between the walls of the tablet and the walls of the die cavity Glidants
Reducing friction between the particles
To improve the flow properties of the granulations
To prevent adherence of the granules to the punch faces and dies
Dissolution (enhancers and retardants)
Flavoring agents Essential properties of tablet : Essential properties of tablet Accurate dosage of medicament, uniform in weight, appearance and diameter
Have the strength to withstand the rigors of mechanical shocks encountered in its production, packaging, shipping and dispensing
Release the medicinal agents in the body in a predictable and reproducible manner
Elegant product, acceptable size and shape
Chemical and physical stabilities Powder compression : Powder compression It is defined as the reduction in volume of a powder owing to the application of a forces.
Because of the increased proximity of particle surfaces accomplished during compression, bonds are formed between particles which provide coherence to the powder i.e. compact is formed. Effect of Compression : Effect of Compression When external mechanical forces applied to a powder mass there is reduction in bulk volume as follows
Elastic deformation-e.g. acetyl salicylic acid, MCC
Plastic deformation-at yield point of elastic.
Brittle fracture – e.g. sucrose
Microquashing-irrespective of larger particles, smaller particles may deform plastically. Difference : Difference Compaction Consolidation It is defined as the formation of solid specimen of defined geometry by powder compression.
The compression takes place in a die by the action of two punches, the lower and the upper by which compression force is applied. It is in increase in mechanical strength of material from particle particle interactions. Tablet production : Tablet production Powders intended for compression into tablets must possess two essential properties
The material can be transported through the hopper into the die
To produce tablets of a consistent weight
Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant
The property of forming a stable, intact compact mass when pressure is applied Compression process : Compression process Filling
By gravitational flow of powder from hopper via the die table into die. The die is closed at its lower end by the lower punch.
The upper punch descends and enters the die and the powder is compressed until a tablet is formed.
During the compression phase, the lower punch can be stationary or can move upwards in the die.
After maximum applied force is reached, the upper punch leaves the powder i.e. the decompressed phase.
During this phase, the lower punch rises until its tip reaches the level of the top of the die. The tablet is subsequently removed from the die and die table by a pushing device. Tablet compression machine : Tablet compression machine Hopper for holding and feeding granulation to be compressed
Dies that define the size and shape of the tablet
Punches for compressing the granulation within the dies
Cam tracks for guiding the movement of the punches
Feeding mechanisms for moving granulation from the hopper into the dies Slide 12: Collar locker Single Punch Machine (Tablets) Upper andLower Collar Tablet production methods : Tablet production methods Dry methods
Wet granulation Direct compression : Direct compression Tablets are compressed directly from powder blends of the active ingredient and suitable excipients
No pretreatment of the powder blends by wet or dry granulation procedures is necessary
Machine: fewer manufacturing steps and pieces of equipment
Labor: reduce labor costs
Less process vallidation
Lower consumption of power Direct compression : Direct compression Advantages
Elimination of granulation process
Heat (wet granulation)
Moisture (wet granulation)
High pressure (dry granulation)
Processing without the need for moisture and heat which is inherent in most wet granulation procedures
Avoidance of high compaction pressures involves in producing tablets by slugging or roll compaction
Elimination of variabilities in wet granulation processing
Binders (temp, viscous, age)
Viscosity of the granulating solution (depend on its temp),
How long it has been prepared, Direct compression : Direct compression Advantages
Rate of binder addition and kneading can affect the properties of the granules formed
The granulating solution, the type and length of mixing and the method and rate of wet and dry screening can change the density and particle size of the granules, which can have a major effect on fill weight and compaction qualities
Type and rate of drying
can lead not only to critical changes in equilibrium MC but also to unblending as soluble active ingredients migrate to the surfaces of the drying granules
More unit processes are incorporated in production, the chances of batch-to-batch variation are compounded Direct compression : Direct compression Advantages
Prime particle dissociation
Each primary drug particle is liberated from the tablet mass and is available for dissolution
Disintegrate rapidly to the primary particle state
Uniformity of particle size
Greater stability of tablet on aging
Fewer chemical stability problems would be encountered as compared to those made by the wet granulation process Direct compression : Direct compression Concerns
Excipient available from only one supplier and often cost more than filler used in granulation
Lack of material knowledge
Physical limitation of drug
No flow ability
Physical characteristics of materials (both drug and excipient)
Size and size distribution
Shape and surface
Lot to lot variability
Coloring Direct compression fillers : Direct compression fillers Common materials that have been modified in the chemical manufacturing process to improve fluidity and compressibility Soluble fillers : Soluble fillers Lactose
Spray dried lactose
Nutab: 95.8% sucrose, 4% convert sugar
Di-Pac: cocrystallization of 97% sucrose and 3% modified dextrin
Emdex: spray crystallized
Maltrin Insoluble fillers : Insoluble fillers Starch
Spray dried starch
Microcrystalline cellulose (Avicel)
Inorganic calcium salts
Dicalcium phosphate (Emcompress or DiTab)
Tricalcium phosphate (TriTab) Heckel equation : Heckel equation Heckel plot is density Vs applied pressure.
Follows first order kinetics.
As the porosity increases the compression force will increase.
The Heckel equation is described as follows. It is based on the assumption that powder compression follows first-order kinetics, with the interparticulate pores as the reactant and the densification of the powder bed as the product.
D= relative density of a powder
P=compact at pressure P.
Constant k = measure of the plasticity of a compressed material.
Constant A =die filling and particle rearrangement before deformation and bonding of the discrete particles.
Thus, a Heckel plot allows for the interpretation of the mechanism of bonding. Kawakita equation : Kawakita equation The Kawakita equation is described as follows. This equation describes the relationship between the degree of volume reduction of the powder column and the applied pressure.
The basis for the Kawakita equation for powder compression is that particles subjected to a compressive load in a confined space are viewed as a system in equilibrium at all stages of compression, so that the product of the pressure term and the volume term is a constant.
C = degree of volume reduction of a powder compact at pressure P.
constants (a and b) =evaluated from a plot of P/C versus P.
a= total volume reduction for the powder bed [carr’s index]
b= constant that is inversely related to the yield strength of the particles.
The data from this study were modeled via the Kawakita equation in an attempt to evaluate the relationship between the volume reduction and applied pressure for each studied DC binder. Slide 29: Jay swaminarayan Slide 30: Best wishes for bright future