processing of tablets

Question 1

there are many tpes of tablets like effervescent, soluble, chewable etc. other than inert what must the excipients of these tablets be?

Answer 1

excipients must be soluble to avoid gritty texture of insoluble particulates.

Question 2

what are the advantages of tablets?

Answer 2

tablets provide accurate dosing, convenient, good physicochemical stability, tailored release of drug, mass production, simple and cost effective and well accepted.

Question 3

what are some of the disadvantages of tablets?

Answer 3

unsuitable for patients with swallowing difficulty, can be difficult to prepare, bitter taste, not good for drugs with low solubility, may require coating if sensitive to water or oxygen.

Question 4

what are the essential properties of tablets?

Answer 4

accurate and uniform dose, recognisable, withstand pressures of processing and handling yet rapidly breakdown when ingested, reproducible dissolution rate, moisture and temperature stability.

Question 5

for particulate systems to be made into tablets, three vital properties are required, what are these?

Answer 5

particles must be sufficiently free flowing, particles must cohere to form a compact of adequate strength when subjected to a force, adhesion of the tablet must be avoided.
unfortunitely active ingredients rarely possess these essential properties so excipients are required.

Question 6

whats the process of making a tablet?

Answer 6

weighing, dry mixing, granulation, tabletting, quality control check, coating, quality assurance check.

Question 7

what does the qulity assurance check involve?

Answer 7

checking dissolution and disintegration of tablets to ensure reliability of the formulation

Question 8

how are tablets produced?

Answer 8

tablets are produced in machines using a dye and a punch to ensure quality control - the press can be embossed with structures or logos for accountability.

Question 9

whats the principal of every tablet machine?

Answer 9

powder is filled to a specific depth in the die, formulation is compressed between two punches, compression force is ended by removal of the upper punch, the lower punch then moves upwards to eject the tablet. the presses can be subdivided into single punch presses or rotary presses.

Question 10

how do single punch presses work?

Answer 10

movement is controlled by an eccentric cam. single punches are used when developing formulations and for early batches due to limited availability of the drug. it has slow production rates and is used in research and developement laboratories. the feed shoe feeds powder into the die by moving over the die the feed shoe then retracts and the upper punch descends so compaction occurs. the upper punch then ascends and lower punch ascends to release tablet from diethe feed shoe then sweeps the tablet off the die table and the cycle repeats.

Question 11

how do rotary table presses work?

Answer 11

commercial manufacture of tablets occurs on rotary tablet machines. its a production belt of dies in a line being filled, compressed and released by movement along a conveyor belt.

Question 12

when compaction occurs particles undergo rearrangement to form a less porous structure, what can this lead to?

Answer 12

fragmentation
deformation elastic is reversible whilst plastic is irreversible
bonding through solid bridges, intermolecular forces and or mechanical interlocking

Question 13

what are the 3 stages of compression of a powder bed?

Answer 13

rearrangement of the powder bed upon application of a stress
deformation of powders due to applied stress
bondng of compressed powders

Question 14

what is the rearrangement stage of tablet compression?

Answer 14

at low levels of stress, upon application of initial stress the powder bed undergoes densification. the particles rearrange to minimise free space between particle. the extent of densification is dictated by the particle size distibution and the frictional forces that operate between particles. as pressure increases relative particle movement is not possible and deformation is therefore induced.

Question 15

whats the deformation stage of compression?

Answer 15

when particles are so closely packed that no filling of voids can occur a further increase of compression force causes the powder to undergo deformation. at this point further reduction in the compact volume results in elastic, plastic or brittle fragmentation and deformation of particles. this can create permanent changes in the shape of the material. the physicochemical and mechanical properties of the powders affect the nature and type of deformation.

Question 16

whats elastic deformation?

Answer 16

when force is applied particles are compressed into a new shape, once force is removed it returns to its original shape.

Question 17

whats brittle deformation?

Answer 17

when force is applied the shape shatters and cannot be recovered.

Question 18

whats plastic deformation ?

Answer 18

when force is applied a new shape is formed - this stays in place once the force is removed. plastic deformation occurs when stress causes the particles of a powder bed to change size/shape - this is not reversible once the stress is removed

Question 19

what happens when a stress is apllied to the powder bed?

Answer 19

powder reaches its yield stress point where particles can realign in a pattern shaped by the exterior stress on the powder bed. part of the mechanical energy durig plastic deformation is converted into heat, the remainder is stored withing the microstructure of the particles as a change in its internal energy.

Question 20

what happens in the bonding stage of compression?

Answer 20

following application of a sufficient stress and deformation, inter particle bonding occurs resulting in the production of a tablet. it is a process by which consolidated powders are bonded together under pressure.

Question 21

what are the dominant mechanism of bonding in tablets?

Answer 21

intermolecular forces - van der waals hydrogen bonding and electrostatic forces
solid bridges - formed by either melting, diffusion between surfaces or recrystallisation of soluble materials in compacts.
mechanical interlocking - particles with rough texture and shape can form bonds by mechanical interlocking.

Question 22

whats involved with direct compression?

Answer 22

particle size reduction through milling, dry mixing of api with excipients, then compression.

Question 23

what is dry mixing?

Answer 23

powders must be well mixed to ensure drug content uniformity, it must be ensured all ingredients are free of lumps and agglomerates, sieving raw materials makes the process more reliable and reproducible.

Question 24

what are the types of blenders available for dry mixing?

Answer 24

v-cone blender, double cone blender, ribbon blender and bin blender.

Question 25

what is the procedure of direct compression?

Answer 25

using the desired particle size of the active ingredient, a compressible vehicle is blended with the active and additional excipients required, the blend is then compressed - common compressible vehicles are microcrystalline cellulose, starch and anhydrated lactose.

Question 26

what is granulation?

Answer 26

granulation is the process by which primary powder particles adhere to form large multiparticulate entities called granules. bonds are formed either by compression or a binding agent. powder is more difficult to compress into a tablet than granulated materials.

Question 27

most of the industry employs wet granulation, what is this?

Answer 27

wet granulation includes wet massing, spray granulation and high shear granulation.

Question 28

why do we granulate?

Answer 28

granulation produces uniform normalised particles with good flow properties, increased compressability, resistance to agglomeration and segregation and reduction in dusting. the granulation process produces large agglomerates. plasticisers and binders are added for compressibility and to resist segregation.

Question 29

the polymer binder distribution is used to improve compressability, what interactions does this allow for wet granules?

btw for dry granules its granule-granule interaction and for spray granules its polymer-polymer interaction as the granules are fully coated with the polymer here.

Answer 29

for wet granulation you can get granule-granule, polymer-polymer or granule-polymer interactions.

Question 30

whats the process of wet granulation?

Answer 30

grind the drug down, blend with a binder and intragranular excipients, put in a mixer/granulator, pass through a wet screen, dry in a fluidised bed dryer, blend with extra granular excipients and finally compaction.
wet granulation is a labourous expensive process and the drug particles experience extensive processing.

Question 31

what drives the particle-particle bonding during initial wet granulation?

Answer 31

particle-particle bonding is driven by surface tension and the adhesion and cohesion forces between particles. these adhered particles form a nucleus for further enlargement of granules. liquid bridges consequently develop between particles which may lead to solid bridging and an increase in tensile strength. ideally the granulating liquid is a mild solvent of an excipient powder and increases solid bridging.

Question 32

why are there only a few granulating solvents available for pharmaceutical granulation?

Answer 32

we cannot eliminate all of the solvent upon drying.

Question 33

what granulating solvents are used?

Answer 33

water, ethanol and isopropanol, polymer solutions are generally used as binders - these include gelatin, starch and synthetic polymers like pvp.

Question 34

outline the process of wet granulation?

Answer 34

powder is sprayed with binder droplets, liquid bridges then form between particles, subsequently becoming solid bridges creating a snowball structure.

Question 35

outline the process of spray granulation?

Answer 35

powder is sprayed with spray droplets causing raising then solidification to a layer build up forming an onion structure.

Question 36

what are the intragranular excipients of wet granulation?

Answer 36

api, filler, binder and disintegrant.

Question 37

what are the extra granular excipients of wet granulation?

Answer 37

lubricant, glidant, more disintegrant.

Question 38

why are there 2 disintegrants in wet granulation?

Answer 38

the intragranular disintegrant helps the individual granules break up whilst the extra granular disintegrant helps the granules break apart from each other.

Question 39

whats the slugging method of dry granulation?

Answer 39

powder blends that cannot be easily compressed due to poor flow or compression properties, or if heat or moisture sensitive materials are involved, slugging may be used. the formulation ingredients are mixed and precompressed on a table press which operates at a significantly higher pressure, the formed slug is consequently ground to a uniform size and compressed into a tablet.

Question 40

whats dry roller compaction?

Answer 40

granulation can be achieved by passing powder between two rollers that compact the material at much higher pressures than a tablet press. low density materials often require roller compaction to achieve sufficient bulk density to allow tablet compression. it produces sheets or wide ribbon of material which is then milled to produce granules. a hammer mill is generally used to break up the compacts.

Question 41

what are the advantages of dry granulation rather than wet granulation?

Answer 41

economical, less equipment and space, eliminate addition of moisture and heat, can cope with a range of materials, process is easily scaled up, mechanical strength of the product is uniform.