MDM: Tablets

Question 1

What are tablets?

Answer 1

A solid preparation manufactured by compressing uniform volumes of particles which contain a single dose of one of more active ingredients and excipients.

Question 2

What are advantages of tablets?

Answer 2

• Convient - to carry/ store
• Good patinet compliance
• Acurate dosing
• chemical, physical and microbial stability
• Generally cheap, robust and elegent

Question 3

Disadvantages of tablets

Answer 3

• Generally systemic delivery
• poor bioavailability
• must be swallowed
• local irritation - GI mucosa
• Extensive developmental work

Question 4

What are the basic steps taken when forming a tablet?

Answer 4

Question 5

When forming a tablet what are the ideal properties for a powder blend?

Answer 5

• Homogenous - doesn’t segregate
• Free flowing - freely flows through tablet machinary
• Adheres and coheres
• doesnt adhere to tablet tooling

Question 6

What are examples of excipents included in tablets?

Answer 6

• Binder
• Distigrant
• Lubricant
• Diluent
• Glidant
  *

Question 7

What is the role of a diluent and some examples?

Answer 7

Increases tablets bulk density and acheive required strength

Lactose, sucrose, mannitol, glucose, Calcium hydrogen phosphate, MCC

Question 8

What are examples of lubricants and their role

Answer 8

Reduce friction between tablet and machinary during manufacture

Magnesium sterate and sodium steryl fumarate

Question 9

What are examples of binders and their roles

Answer 9

Improves mechanical strength by binding particles

PVP, gelatine, sucrose

Question 10

What is the role of distigrants and some examples

Answer 10

Promote rapid tablet distigrant

Starch, cellulose, PVP,

Question 11

What are example of glidants and their roles?

Answer 11

Improves powder flow by reducing intra-particular friction

silica, magnesuim sterate, talc

Question 12

What are methods used to determine powder flow?

What do these methods tell you?

Answer 12

• Flow through an orfice - flow rate
• Angle of response - inter particular cohesion
• Bulk density - percentage compressability and friction

Question 13

What is powder flow dependent upon?

Answer 13

• Particle size, shape and density

Question 14

A powder has poor flow characteristics. What could be done to sort this?

Answer 14

• Increase particle size and reduce size distribution
• Change particle size and texture e.g. during spray drying, cyrstallisation
• Change surface forces - e.g. add glidant
• Alter process conditions e.g. vibration assisted hoppers

Question 15

What are examples of equipments used to mix powders?

Answer 15

• tumbling
• high speed mixer granulators
• fluidised bed mixers
• agitator mixers

Question 16

What is powder mixing depent on?

Answer 16

• shape
• size
• density of particles
  *

Question 17

What improvement could be done to improve powder mixing?

Answer 17

• Granulation
• Reduce particle size distribution - e.g. sieving or milling
• controlled crystilisation - particular shape and sized crystals
• Choose excipents with similar density to API
• Reduce blending movement
• Equipment - reduce time in hoppers, reduce transfer

Question 18

When forming tablets what are the 2 methods that can be used?

Describe breifely these

Answer 18

Direct compression - drug and excipents mixed

or granulation - primary powder particles adhere to form granules

Question 19

What are advantages and disadvantages of direct compression?

Answer 19

Advantages:

• Faster drug dissolution
• Reduction in manufactuing time and costs

Disadvantages:

• powder segregation
• poor compaction properties
• poor colour uniformity
• specialist fillers and binders required
• powder must have good flow properties

Question 20

Advantages and disadvantages of granulation

Answer 20

Advantages:

• increases compactiabilty
• improved colour uniformity
• improves powder flow
• increases bulk density
• improves homogeneity and prevent segregation

Disadvantages:

• increases in production time and costs
• may cause hydrolysis of drug

Question 21

Describe 2 other granulating methods

Answer 21

• Fluidised bed drier - spray drying using a binder solution
• Dry granulating - using pressure to form compacts

Question 22

What are the benefits/ negatives of spray drying and dry granulating?

Answer 22

Spray drying - produces high quality granules - good homeogenity, flow and compactability. Time consusing

Dry granulation - no hydrolysis of drug

Question 23

What is powder compression?

Answer 23

Pushing particles into close proximaty to each other by using confined compression

Question 24

What are the 3 stages involved in powder compression to form a tablet?

Answer 24

1. Die filling
2. Tablet formation (compression of tablet from upper and lower die)
3. Tablet ejection

Question 25

How does a tablet pressor work? What are the differences between both? What are they used for?

Answer 25

1. Hopper filed with powder and and fills dies which are then compressed by upper and lower dies before being ejected 2. Single punch tablet press - one set of tools and small output. 3. rotary tablet press - multiple sets of tools and high out put 4. Single tablet punch used to produce tablets for clinical trials and during formulation development

Question 26

Why would we coat a tablet?

Answer 26

* Protect the drug * mask taste * ease of swallowing * improves appearance * rapid idnetificartion * increases bulk * modified release characteristics * ease of handling

Question 27

What are examples of types of tablet coatings?

Answer 27

* film * sugar * compression

Question 28

Describe film coating

Answer 28

* most common * ploymers, platisticizers, colourants * sprayed onto rotating tablet * immediate (non functional) - water soluble * functional - modified - PH 5 -6

Question 29

Describe sugar coating

Answer 29

* sucrose based syrup * sugar coating pan (6 stages - sealing, subcoating, smoothing, colouring, polishing, printing) * readily water soluble - distigrant * generally immediate release

Question 30

Describe compression coating

Answer 30

compatction of granular particles around tablet core

Question 31

What are the desired attributes of a tablet?

Answer 31

* contains correct dose * consistant size, weight and appearance * drug release controlled and reproducable * sufficent mechanical strength * physical, chemiacal and microbiologically stable * formulated for patient acceptance * packaged appropriately *

Question 32

Why is tablet testing required?

Answer 32

* To ensure the patient receives a tablet which contains the required amount of drug substance in a form in which it can exert its full pharmacological action. * to ensure it is microbiologically stable * to ensure the AI is released over a specified time * ensure mechanical strenght is sufficent to avoid it crumbling/ breaking on handling

Question 33

What are examples of drug tests carried out?

Answer 33

* Uniformity of weight

Question 34

Describe uniformity of weight testing

Answer 34

* equal to or greater than 25mg or 25% drug coc * individually weigh 20 tablets and determine the mean * Not more than 2 tablets should deviate from the mean by particular % and no tablets should deviate by twice the % * More acurate with higher drug conc 1. ≤ 80mg - 10% 2. \> 80mg /\< 250mg - 7.5% 3. ≥250mg - 5%

Question 35

Describe uniformity of content

Answer 35

* Done if less than 25mg or less than 25% drug content * using appropriate analytical technique determine drug content of 20 tablets * Drug content of each tablet should fall between 85% - 115% of average content * One tablet allowed to be between 75% - 125% of avergae content * if one tablet falls out with limits re test another 20

Question 36

Describe friability testing

Answer 36

* Friabilitor used - Mimics forces encountered during handling * tablets must resist friability to ensure appearance and dose is maintained * if less or equal to 650mg - 6.5g of whole tablets tested * if more than 650mg - 10 tablets tested * No more thn 1% mass loss allowed and no chips or cracks allowed

Question 37

Describe fracture resistance testing

Answer 37

* The resistance to crush tablet - measured by force. * Tablet placed against platen, load applied along diameter by movable platen. Tablet cracks along diameter into two pieces of similar size and force recorded. * Record mean, minimum and maximum forces (Newtons). RGU: Mean force - 40 – 100 Newtons

Question 38

Describe distigratin testing

Answer 38

* Determines if tablets disintigrate in prescribed time * 6 tablets in purified water at 37°C +/- 2 for 15 mins * if 1 or 1 fail test further 12. 16/ 18 must distigrate in required time * depends on type of tablet e.g. coated - 60 mins *

Question 39

Describe dissolution testing

Answer 39

* Tablet placed in dissolution medium in stirred vessle at 37 +/- 0.5 * more than 70/ 75% of drug released after 45 mins

Question 40

What are problems that can occur during tableting?

Answer 40

* low mechanical strength * weight/ dose variations (granulate?) * capping - top of tablet fractures/ breaks * lamination - tablet breaks into more than 2 distinict horizontal layers * sticking - powder sticks to punch * picking - particular sticking where powder sticks wihtin letters/ logos of punch * chipping - breaking of edge of tablet

Question 41

What tablet classes is there?

Answer 41

* immediate release: rapid drug release * modified release: slower/ varied drug release * prolonged release: released slowly over a long period of time * ­Pulsatile release: Released in two or more pulses * Delayed release: Released some time after administration

Question 42

What are types of immediate release tablets?

Answer 42

* distigrating * chewable * effervescent * compressed lozingers * sublingual and buccal tablets

Question 43

Describe distigratning tablets

Answer 43

* Most common tablet type - intended for swallowing whole. * Drug release: disintegration -\> dissolution -\> absorption * Disintegration rate: dependant on several formulation and production factors. * Dissolution rate: limited by drug factors such as solubility and particle size. * Absorption rate: lipophilicity * Examples: Paracetamol, Ibuprofen.

Question 44

Describe chewable tablets

Answer 44

* Mechanical disintegration – no disintegrant * Drug dissolves in stomach * Rapid effect, no water required, for patients with difficulty swallowing * Flavourings and colourings commonly used * Vitamins, Gaviscon

Question 45

Describe effervscengt tablets

Answer 45

* Releases carbon dioxide – facilitating disintegration and dissolution (reaction between carbonate / bicarbonate and acid such as citric or tartaric acids) * Rapid drug action * Analgesics, vitamins

Question 46

Describe compressed lozengers

Answer 46

* Slow drug release - No disintegrant * Systemic and local drug delivery * Filler and binder – water soluble and acceptable taste e.g. carbohydrates / sugars * Colouring and flavouring * High pressure – increased hardness and low porosity. * e.g Strepsils, Nicotine

Question 47

describe buccal/ sublingual

Answer 47

* Rapid systemic delivery avoiding first pass liver metabolism * Subligual – under tongue / Buccal – side of cheek / between upper lip and gum. * Small, porous, disintegrant (buccal). * Slow release – polymers 1 – 2 hrs * e.g. Nitroglycerin, Loratadine, Nicotine (Nicotinell), Nytroglycerin (Nitrostat).

Question 48

1. Tablets too soft? 2. Tablets not disintegrating? 3. Tablets breaking apart after manufacture? 4. Active not being released from tablet during dissolution test? 5. Powder will not flow correctly?

Answer 48

1. binder or less distigrant 2. add distigrant 3. Add binder 4. Distigrant 5. glidant 6. granulation