Powders, tablets and capsules Flashcards
What are advantages of powder formulation
Chemically more stable than liquid formulations
Preferred form of administration
May provide faster drug dissolution than tablets or capsules
Easier to swallow for very young and elderly populations
What are disadvantages of powder formulation
Accurate dosing is difficult to achieve
Less convenient to administer and transport
Difficult to mask taste and grittiness
Difficult to minimise drug irritation and drug degradation
Barrier packaging required for drugs that are volatile, deliquescent hygroscopic or readily oxidised
What are reasons for reducing particle size
Usually to micron size
For homogenous mixing
To minimise segregation of powders in a powder mix
* Narrow size distribution
* Prevent demixing
To improve drug dissolution rate and bioavailability
To minimise powder grittiness and enhance product acceptance
To optimise drug delivery to deep lungs
What are reasons for increasing particle size
Granulation
Maintain homogeneity of powder mix and reduce demixing
Improve handling
* Powder flow
* Reduce occupational hazards
* Reduce caking and hardening on storage
Improve compaction into tablets
Improve wettability
* Granules are larger to attract wetting agent, becomes close in proximity of wetting agent
Increase bulk density to reduce packing volume and costs of transport
* Powders stick to everything, granules reduce sticking
What is wet granulation
Mix powder with granulating fluid to form wet mass
Mechanisms of particle bonding
Formation of solid bridges between particles
Attractive van der Waals forces between solid particles
Mechanical interlocking of solid particles
Advantages of spheronisation
Same as other granules but smooth surface
* Spherical shapes allows for better flow
Smooth surface facilitates uniform thin layer coating
* Allows for mixing of incompatible ingredients and manufacture of modified release dosage forms
How are dry granulations made
Roller compaction
Milling of sheets/ flakes/ slugs
What is mixing
What is convective mixing
One part of powder bed moves relative to another part
Creates segregated mixture
Small particles with large particles
What is shear mixing
A layer of powder particles moves relative to another layer
This creates an ideal mixture
What is diffusive mixing
Individual powder particles move relative to each other
This creates a random mixture
* Requires velocity to obtain this mixture
* Introduce void space
How do you minimise demixing
Use narrow particle size range or ensure all particles are below 30microns
Control particle shape
Use particles of similar density
Use granulation or ordered mixing
Reduce vibration when processing post-mixed powders
Use one-stop operational equipment
What are the advantages of different drying processes
What are the disadvantages of
Fluidized bed dryin
Microwave
Spray
Freeze
What are the advantages for tablet formulation
Convenient and accurate dosing
Provision for identification
* Different colours
* Indentation
* Score lines
More stable compared to liquids
Controlled drug release possible
Cost effective industrial manufacture
Versatile design
What are the disadvantages for tablet formulation
Peroral BA may not be as good as liquids
Inappropriate for patients who have difficulty swallowing
Does not provide for flexible dosing compared to liquids for paedriatrics
Wet granulation
Dry granulation
Direct compression
Advantages of direct compression
Simplicity of manufacture
No water and drying processes
Faster disintegration and dissolution
Disadvantages of direct compression
Requires a powder with adequate flow and good compressibility
Relatively large particles required
Challenging for
* Drugs with low dose to achieve content uniformity
o <10mg
* Drugs of high dose to achieve good flow and compressibility
o >50mg
Require diluents of specialised grades
Reasons for coating tablets
Protection
Masking of taste
Improve aesthetics
Aid in identification
Confers added strength
Impart functional properties
What are film coating
Uses polymers as coating agents
* Thin layer of polymer film deposited over tablet cores by atomisation of coating liquid
Controlled release function
Enteric coating
* Protect drug from being released in stomach
Film vs sugar coating
Disintegrating tablets
Designed to be swallowed, disintegrate and release entire drug load over a short period in the GIT
Also known as plain or conventional tablets
Chewable tablets
Tablet disintegration in oral cavity
Fast tablet disintegration
o For rapid local or systemic action
Effervescent tablets
Disintegrate and dissolve in water prior to oral administration
Benefit from faster stomach emptying
Lozenges
Designed to dissolve slowly in the mouth
For local action
Sublingual tablets
For fast disintegration, drug release and absorption in the sublingual cavity to avoid first pass metabolism
Buccal tablets
Drug released and absorption in the buccal cavity to avoid first pass metabolism
Quality standard and compendial requirements
Physical properties - defects
Defects in film coating - picking, twinning, mottling, erosion, bridging
Uniformity of dosage units
Dissolution test
Disintegration test
Friability test
Hardness test
Examples of diluent
Lactose
Mannitol
Microcrystalline cellulose (MCC)
Calcium phosphate
Calcium carbonate
Examples of binders
Solution binder
Gelatin
Glucose
Starch
Dry binder
MCC
Crosslinked polyvinyl pyrrolidine
Methylcellulose (MC)
Examples of disintegrant
Starch
MCC
Crospovidone
Croscarmellose sodium
Sodium starch glycolate
Sodium bicarbonate plus citric and tartaric acids
Examples of glidant
Colloidal silica
Magnesium stearate
Talc
Examples of lubricant
Magnesium stearate
Polyethylene glycol
Sodium lauryl sulfate
Liquid paraffin
Examples of antiadherent
Magnesium stearate
Talc
Starch
Advantages of capsules
Similar to tablets
Gelatin shell provides taste masking and drug protection
More versatile and aesthetically pleasing
Disadvantages of capsules
Little flexibility of dosing
Potential for gastric irritation for highly soluble drugs
Two step manufacture
Filling equipment is less efficient
More readily tampered
Ideal features of capsules
Must not react with gelatine
Must not contain high level of free moisture
Unit dose must fit into capsule
Capable of being filled uniformly
Stable over storage period
Drug release kinetics comply with specifications
Excipients of powder formulated capsules
Diluent
Glidant
Lubricant
Disintegrant
Wetting agent
Excipients of liquid formulated capsules
Lipophilic Solvents
Solubilisers
Surfactants
Emulsifiers
Quality standards and compendial requirements for capsules
Physical defects
Uniformity of dosage units
Drug content
Disintegration test
Dissolution test
What are hard shells made out of
Gelatin
Colourants/ opacifying agents
Plasticisers
Wetting agents
What are soft shells made out of
Gelatin
Plasticiser
Water
Colourant/ opacifying agents
Preservatives
