compaction

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 High stability 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 Binders To bind powders together in the wet granulation process To bind granule together during compression Disintegrants To promote breakup of the tablets To promote rapid release of the drug Lubricants 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 Antiadherants To prevent adherence of the granules to the punch faces and dies Dissolution (enhancers and retardants) Wetting agents Antioxidants Preservatives Coloring agents 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 Repacking Particles deformation 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 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. Consolidation 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 Powder fluidity 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 Powder compressibility 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. Compression 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. Ejection 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 and Lower Collar

Role of lubricants :

Role of lubricants Lubricant functions in tablet manufacture. Prevent adhesion of the tablet material to the surface of the dies and punches. Reduce inter particle friction. Facilitate the ejection of the tablets from the die cavity. May improve the rate of flow of the tablet granulation. Commonly used lubricants include: talc, magnesium stearat , calcium stearate , stearic acid, hydrogenated vegetable oils and (PEG). Most lubricants, with the exception of talc, are used in concentrations less than 1%. When used alone, talc may require concentrations as high as 5%. Lubricants are in most cases hydrophobic materials. Poor selection or excessive amounts can result in “waterproofing” the tablets, resulting in poor tablet disintegration and or delayed dissolution of the drug substance

Slide 17:

Anti adherants: reduce sticking and adhesion of the tablet granulation or powder to the faces of the punches or to the die walls. Glidants promote the flow of the tablet granulation or powder materials by reducing friction among particles

Tablet production methods:

Tablet production methods Dry methods Direct compression Dry granulation Wet 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 Advantages Economy 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 Color Dissolution rate 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 Procedure conservation Machine investments Lack of material knowledge Physical limitation of drug No compressibility No flow ability Physical characteristics of materials (both drug and excipient ) Size and size distribution Moisture Shape and surface Flowability Density Lot to lot variability Dusting problem 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 Sucrose Nutab : 95.8% sucrose, 4% convert sugar Di-Pac: cocrystallization of 97% sucrose and 3% modified dextrin Dextrose Emdex : spray crystallized Sorbitol Mannitol Maltodextrin Maltrin

Insoluble fillers:

Insoluble fillers Starch Starch 1500 Spray dried starch Celulose Microcrystalline cellulose (Avicel) Inorganic calcium salts Dicalcium phosphate (Emcompress or DiTab) Tricalcium phosphate (TriTab)

Factors affecting strength of compressed tablets:

Factors affecting strength of compressed tablets Moisture Air entrapment Binder strength Compression force Process variables

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. Where 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. where 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.