solid oral dosage forms pt 2

What is the key difference between conventional and disintegrating tablets?


Disintegration → dissolution → absorption

What are disintegrating tablets?

Conventional or plain tablets

What steps follow disintegration in tablet drug release?


Dissolution then absorption

What can be rate-limiting for bioavailability in tablets?


Disintegration, dissolution, or absorption

What must occur before absorption from a chewable tablet?


Disintegration in mouth but drug must be swallowed before absorption can happen

How do chewable tablets contribute to onset of action?


Rapid onset

Who are chewable tablets useful for?


Difficulty swallowing tablets

What is generally not included in chewable tablet formulations?


Disintegrants

. What excipients are often needed in chewable tablets?


Flavouring agents

What gas is released in effervescent tablets?


CO₂ during dissolution in water

How is CO₂ generated in effervescent tablets?


Carbonate + weak acid

What effect do effervescent tablets have on onset?


Rapid drug action

How does sodium bicarbonate affect gastric emptying?


Lowers stomach pH, increases emptying —> can lead to side effects

What are generally not needed in effervescent tablets?


Binders

What formulation aid is commonly needed in effervescent tablets?


Flavourings

What packaging consideration is important for effervescent tablets?


Moisture protection

How are compressed lozenges dissolved?


Slowly in mouth

Where does drug dissolve from a compressed lozenge?


In saliva

What is generally not required in compressed lozenges?


Disintegrants

What extra formulation considerations do compressed lozenges need?


Flavouring and colouring

What properties should fillers/binders have in lozenges?


Water-soluble, pleasant taste

Give an example filler for compressed lozenges.


Sugar

Where does drug release and absorption occur for sublingual/buccal tablets?


Mouth

How do sublingual/buccal tablets avoid first-pass metabolism?


Direct systemic absorption

What is the main advantage of sublingual/buccal delivery?


Rapid systemic effect - porous to facilitate disintegration

Why are mucoadhesive polymers used in buccal tablets?


Prolong residence time

How can hydrophilic polymers provide controlled release buccally?


• High MW hydrophilic polymers attract water to form gum —> controlled release

What is modified release drug delivery?


Controlled drug release

What is the aim of modified-release systems?


Deliver API at desired rate/place (specific points in GI)/time

What therapeutic benefit can modified release provide overnight?


Maintain concentration in therapeutic range

How can modified-release systems affect dosing?


Reduce dosing frequency - chronotherapy

How can modified-release systems affect side effects and adherence?


Fewer side effects, better adherence

Where in the body can modified-release systems target drug release?


Specific GI tract locations

What are the two main approaches to modified release?


release modifying ingredients added to matrix

or application of modified release coating

What are other names for prolonged-release tablets?


slow release, extended release, sustained release, controlled release

What goal do prolonged-release tablets achieve?


Longer drug action

What duration is typically aimed for with prolonged release?


Over 12 hours-24hr

What blood concentration profile is characteristic of prolonged release?


Therapeutic level maintained longer

Which drugs are most suitable for prolonged release?


BCS class I

. What type of matrices are used in hydrophilic matrix systems?


Swellable soluble matrices

What happens when hydrophilic polymers contact water?


Form gel

. What are advantages of hydrophilic matrix systems?


Good safety and drug loading

What problem can occur with hydrophilic matrices?


Dose dumping - food effects can be an issue (taken on full stomach, empty stomach etc)

How does an insoluble polymer matrix control release?


Drug trapped in inert polymer

How is drug released from insoluble matrices?


Through pores in matrix

Matrix remained intact throughout GI tract

What controls release rate in insoluble matrices?


Pore size and tortuosity

What happens to release rate as drug content falls in matrix systems?


Release decreases

What is the rate-limiting step in diffusion-controlled systems?


Drug diffusion

What is diffusion based matrix system?


pores present in matrix

What membrane feature controls release in reservoir systems?


Thin, water insoluble membrane

What happens in diffusion controlled release system?

• Liquid penetrate dosage form, dissolving drug, drug diffuses our of dosage form

What factors affect diffusion rate in membrane-controlled systems?


Area, distance, diffusion coefficient

What is the rate-limiting step in dissolution-controlled systems?


Drug dissolution

Which drugs are suited to dissolution-controlled release?


Poorly soluble drugs

How can water-soluble drugs be modified for dissolution control?


• Water soluble drugs can be modified into poorly soluble salts or coating drug particles

How can multiple release rates (pulsatile) be achieved by coatings?


Different thickness/solubility

. Why are dissolution-controlled systems used in delayed-release tablets?


GR Coating dissolves at higher pH

What controls release in erosion-controlled systems?


Rate limiting step: Matrix erosion

What happens when erosion-controlled matrix material is removed?


• Matrix material liberated from surface of tablet, leading to exposure of drug to GI fluids

What Kinetic is erosion controlled release?

0 order

. Which polymers are commonly used in erosion-controlled systems matrix?


• Matrix lipid, waxes, gelatine polymers

What is the rate-limiting step in osmotic systems?


Water influx

• Rate limiting step is flow of liquid into dosage unit, driven by difference in osmotic pressure

What drives water entry into osmotic systems?


Osmotic pressure difference

What membrane is used in osmotic-release systems?


Semipermeable membrane

How does drug leave an osmotic-release device?


• Osmotic transport of liquid in allows dissolution of drug, which leaves through single orifice/pores via connective transport

Why are gastroretentive formulations used?


• Dosage form retained in stomach —> absorption in upper GI tract maximised

What are the 3 types of gastrorentention systems?

Mucoadhesion

Floating

Size increasing systems

Where is a gastroretentive dosage form retained?


Stomach

What triggers gastro-resistant delayed release?


Predetermined pH - membrane dissolves/disintegrates then

Where is drug released from gastro-resistant systems?


Small intestine

What is the aim of colonic drug delivery?


• pH responsive polymers to target colon

What is one colonic-trigger mechanism?


Gut bacteria degradation

(e.g resistant starch), more reproducible, still experimental

What polymer type may be used for colonic delivery


: pH-responsive polymers

Which drug became the first FDA-approved 3D printed tablet in 2015?


Spritam (levetiracetam)

. What advantage does 3D printing provide for medicines?


Adjustable design and dose and shape

. How can 3D printing control release profiles?


Layer-by-layer printing

What tests are commonly performed on tablets?


Content uniformity, disintegration, dissolution, strength

Compare disintegration and dissolution testing.


Disintegration testing	Dissolution testing
Mimics disintegration of tablets after oral administration	Release of drug and factors that will affect bioavailability
Agitation of tablets in aqueous medium at set temp	Cumulative drug release measured against time
Time to reach end point measured (tablet no longer visible)	Tablet placed in chamber w/ appropriate dissolution medium (varied depending on intended action)
Not aiming to find in vivo correlation w/ absorption	Stirred vessel - rotating basket method and paddle method
Used in formulation development	Continuous flow methods, arguably most accurate

What is meant by a friable tablett?


Easily eroded during handling

What can friability cause in tablets?


Weight loss and appearance changes

What tablet defect is also checked during friability testing?


Capping

. How is friability assessed?


Weight loss and visual inspection

What weight loss is acceptable in friability testing?


Less than 1%

What is the purpose of fracture resistance testing?


Determine force needed to fracture

What type of compression is used in fracture resistance testing?


Diametral compression

What other name is given to fracture resistance testing?


Crushing strength/hardness testing

. What may different fracture patterns indicate?


Reasons for failure

What are the two parts of a hard capsule?


Cap and body

What materials are used to make hard capsules?


Gelatin/hypromellose, water, colourant

What holds a hard capsule together?


Cap and body indentations

What polymer properties are required for hard capsules?


Non-toxic, soluble, film-forming

For uniformity of weight, what is the percentage deviation for something:

1. More more than 80mg

2. More than 80mg but less than 250mg

3. 250mg or more

Give examples of non-azo dyes used as colourants.


Erythrosine (E127)

indigo carmine (E132)

quinolone yellow (E104)

Give examples of pigment colourants and their colours


• Iron oxide (E172) - black, red, yellow

• Titanium oxide (E171) - white

 

What happens at each step during tablet manufacturing?

. How does dependent capsule filling work?


Capsule body measures powder

. What must occur in dependent capsule filling?


Complete capsule filling

What device is used in dependent capsule filling?


Auger

How does independent capsule filling work?


Powder measured separately in measuring device

Can capsules be partially filled in independent filling?


Yes