Thermal Analysis Flashcards
What is the meaning of melting point (Tm)?
The temperature at which the pure liquid and solid co-exist in equilibrium at 1Atm pressure
What is ‘the latent heat of fusion’?
The amount of heat required to melt a material by breaking bonds
What is polymorphism?
The same molecule having different solid-state structures (diamond and graphite).
Polymorphs have different crystal lattice energies but are chemically identical.
Polymorphs have different solubilities, dissolution rate and bioavailability.
What is the issue with polymorphism in drug development?
*must be sure drug stays in one form throughout whole shelf life
*undesirable polymorph may be toxic
*issues scaling up I.e methods of preparation may change- different solvents, heat generated
What are examples of drugs exhibiting polymorphism?
*carbamazepine
*paracetamol
*ampicillin
What excipients exhibit polymorphism?
*sorbitol
*lactose
What does it mean if a drug is enantiotropic?
The two different forms of the drug have a definite transition point and can change reversibly into one another. At a key temperature, the form stable at low temperatures can convert to high temperature form.
What is a monotropic drug?
When one form is more stable at all temperatures. Unstable polymorph will have a lower Tm. Upon heating no transition is observed.
What is a solvate?
Crystal lattice of polymorph also contains solvent molecules (eg water)
What is the characteristic transition of amorphous materials ?
The glass transition Tg. Below Tg= hard and brittle. Reaction is slow. Above Tg=soft and rubbery. Reaction is faster
What are amorphous materials?
Material that has structure of a liquid but mobility of a solid. They have no melting temperature because have no crystal lattice to be broken.
What is DSC?
Stands for differential scanning calorimetry. It is a thermal analysis method. Measuring heat output and comparing between reference and sample.
What are the two types of DSC?
*Heat flux DSC-direct comparison of reference and sample in same furnace
P= (Ts-Tr)/Rt
p=power
Ts=samaple temperature
Tr=reference temperature
Rt=resistance applied
Power (output of DSC in J/s)
*Power compensation DSC-two separate furnaces
What metal is used to calibrate DSC?
Indium
What does MTDSC stand for?
Modulated temperature differential scanning calorimetry
Benefit of using MTDSC
Easier to observe Tg
Why do we need to know Tg?
To ensure drug is not stored above Tg causing it to crystallise and increase degradation.
Also to control water content (water lowers Tg as it is a plasticiser)-product must be dry enough to exhibit reasonable Tg yet retain water for structure.
Does lowering Tg (increasing water) increase or decrease stability ?
Decrease
How is glass transition measured?
Thermo Gravimetric Analysis (TGA)
*sample heated in controlled manner
*mass loss=water loss
*mass change determined by null-balance principal
What is the difference between TGA and Karl Fischer titration?
*Sample size can be smaller
*Faster
What is microcalorimetry?
Measuring heat in or out of a sample at isothermal temperature (constant temp)
What is thermomechanical analysis (TMA) used for?
*measure dimensional changes in materials (as a function of temp, time isothermally)
*to determine thermal expansion coefficients
*%expansion/contraction
*phase transitions eg Tg
Disadvantages of TMA
Limited to solids I.e unreliable for amorphous materials
What materials can be used for TMA?
*stratum corneum (skin)
*braces
*catheters
*intravaginal rings
What is DMA?
Dynamic mechanical analysis. Used to determine viscoelastic properties of pharmaceutical systems. (Contact lens and heart valves). Stress applied to sample and resultant strain measured as a function of frequency and temperature.
What is stress in terms of DMA?
Force per unit area (Pa) required to deform the sample.
What is strain in terms of DMA?
Amount by which sample is deformed. Also known as amplitude (distance)
What is modulus in relation to DMA?
Resistance of a material to deformation
*storage modulus G’- how much mechanical energy stored in material during deformation recovered when stress released.
*loss modulus G’’-how much mechanical energy lost during deformation (viscosity)
What is phase angle in relation to DMA?
Phase angle between strain and stress phases (tan§(G’’/G’)
What is DMA used for?
*measuring glass transitions Tg
*rate and extent of polymeric curing
*polymer compatibility
*interactions between polymeric components
* interactions between drug molecules and polymeric constituents of pharmaceutical systems like catheters
Why do we need to know mechanical properties of polymeric systems?
*conductance of body fluids (urine)
* prevent rapid release of active agents
