Stability of ASD Flashcards
Definition of ASD
Amorphouse Solid dispersion
Physical formulation methods to enhance the solubility
Amorphous Solid Dispersion and Nanosuspensions
ASD improved dissolution profile
Faster dissolution and Supersaturation
What are the main differences between amorphous and crystalline API
Near order, Tg and thermodyanmic instable amorphous
Near and Far order, Melting point and thermodynamic stableare
What are the properties of polymers
usally high glass transition temperature and high viscosity
What are the steps during the dissolution of crystalline APIs
Disruption of crystal lattic, solvation or hydration of molecules, breakage of solvent/hydrogen bonds to accomadate molecules,
the disruption of crystal lattice is
endothermic
solvation of molecules is
exothermic
Breakage of solvent
endothermic
engery in disolution
endo or exothermic depending on the dominant energies
when do we have poor solubility
high lactic engergy and/ or poor solvatioan
What does it means if there is no lattic energy
better solbility
What is the driving force for crystallization?
the higher supersooling
what does supercooled glasses have?
they have a higher Gibbs energy in comparison with crystalline materiall
Why are amorphous API thermodynamically instable?
Due to their high free energy
How can amorphous API be stabiliziert
with Polymer
increasing the solubility, Miscibility and Kinetic stability
What is mix tg line
it is the tg of the API and that of the polymer, mixture in einer molecule level
when can the mix tg be formed
when the APT has a good solubility in the polymer and mixability
What happend if the solubility of the API is low
it will lead to phase separtaion, due to the different tg
When the ASD kinetic stable
When it is stored below its tg
What happend if the drug load is higher than the solubility line
is will be thermodynamic stable, reducing the solubility
what happend if the drug load is high
it could lead to kinetic stability, but is shouldn’t go above the mix tg , which will lead to the thermodynamic instable state
what does Spring means?
Amorphous API have a high energy state, which leads to a high apparent solubility. Without a stabilizing agent, precipitation will occur
Describe the word parachut in respects of the ADS
Due to adding of the Polymers as a stabilizing agent, there will be an temporary inhibition of precipitation
What’s the different between the apparent solubility and the true solubility
the treu solubility is in the thermody.equilibrium to most stable solid form, whereby the apparent solubility is the unstable form
Which parameters are influnces by the Polymer excipients
API solubility, degree of supersaturation, viscosity, molecular mobility, nucleation, configurational entropy and free energy of ASD
how does the polymer excipient influnces the parameters of the ASD?
API solubility (increase), degree of supersaturation (Decrease), viscosity (increase), molecular mobility (Decrease), nucleation (decrease), configurational entropy (increase )and free energy of ASD (decrease)
What are the effect of the ADS parachut interactions?
Higher activation energy for nucleation
slow crystal growth due to adsorption on crytal surface
API with high tg
they are good so solubilized
Name 4 effects on physical stability of ASD
Glass transition temperature of amorphose drugs and polymers
drug-polymer miscibility
solid solubility of drugs in the polymers
molecular weight of drugs
What are the preparation process, ASD?
Different thermal histories and mechanical stresse.
Using different degrees of drug-polymer mixing and drug mobility in ASD
Production of ASDs
Melting and dyring processes
what affects the stability of the ASD exstrusion
the resistence time, the high temperature
What is the disadvantages of the spray drying ASD?
difficult to fine sovent for both API and polymer
characterization Methods for crystallinity
DCS, XRPD, FTIR-Spectroscopy
characterization Methods for Homogenity
FTIR, NMR
characterization Methods for Interactions
FTIR
Describe how the differential scanning calorimetry works (phases)
Power compensating DSC, Heat flux DSC Measurment
Power compensating DSC
Recording of differential power signal, which is a function of actual sample temperature
Heat flux DSC
Temperature differrents between the sample and reference and it is plotted gainst time
Integration of differences
Transfer into heat flux
Measurement in the DSC
Sample filled up, reference and sample are heated or colled–> temperature diagram
x-ray powder diffraction different between crystalline and amorphous state
Crystalline state: Angle dependent high x-ray intensities detected
Amorphous state: no Bragg Peaks detected
FTIR-spectroscopy used for?
Crystallinity
which other method can be used to check Crystallinity
DSC, XRPD, FTIR spectroscopy
FTIR-spectroscopy advantages
improved signal to noise ratio
faster detection of spectra
improved wave numer accuracy
API-polymer interaction
