Stability of Nanoformulations Flashcards
Why are nanoparticles thermodynamically instable?
Due to their large surface area, without a stabilization ist will leads to formation of agglomearates.lossing the advantges of the larger surface area
what are the two ways to stabilizier nanoparticles?
steric and electrostatic stabilization
Which polymer are used for steric and electrostatic stabilization
non-ionic surfactants, pr unchardged water soluble polymers for steric and ionic surfactants for electrostatic stabilization
Production of Nanoparticles
Top down and Bottow up processes
What kind of particle size do used in both porcessess
TDP: API microparticles
BUP: API molecules
what do you have to create in the TDP:
one has to creat a microsuspension, using high pressure homogenisation to prodcued the nanoparticles
Process in the BUP
- the API solvent mixed with an anisolvent (low solubility of the API). this will lead to precipitation–>nucleation–>growth.
What happend to the crystals in the BUP if there are not stabilisied
it will leads to aggregation
Which guidelines targted the nano-medicine
ICH guideline Q5C for cancer targeting Nontargeted Q1A(R2) and Q1C
Where are the general storage conditions mentioned
ICH Q1A(R2)
What are some application for nanoformulation
oral and perenteral administrations
emerging application: ocular drug delivery
What other instabilities exist during storage or Nanosuspensions
Ostwald ripening
sedimentation/creaming and cakeing
What is ostwald ripening?
It is define as the growth of larger particle at the loss of samll partciles, due to diffusion of the API molecules from the small particles (higherconcentrated areas) to surfacelayer of the big particles (lower concentrated areas)
Was is the results of ostwald ripening?
Precipitation of the API in low concentrated areas
How can ostwald ripening be avoid or slowdown?
having a narrow particle size distribution
low storage temperatures
solidification of suspensions
Why can ostwald ripening be avioded with NPSD?
Small devaition between PSD of particles in system cause low concentration gradients and therefore lower flux
what’s the aim of the top/down bottom-up process?
Lower polydispersity index (PDI) or PSD
What does PDI 1 or 0 means?
PDI 1 means more polydisperse is the sample and 0 menas that just one particle size is present
Effect of the low storage temperatures?
Due to the fact that diffusion is temperature dependent, the low temperatures, the diffusion process is low down and therefore ostwald ripening
Process of solidification of suspensions
Spray drying and Freeze drying
what are reversible agglomeration?
rapid sedimentation/creaming
What’s the consequence of agglomeration?
inconsistent dosing, prevention is very important
How does the electrostatic stabilization works
Around the particle there is a electric doble layer, which is the surface potential of the particles.
Stern layer?
the particles in the stern layer abdsorbed strongly ounter ions, leading to
linear decrease of the potential
Diffuse layer?
wakly bound ions on the particles, leading to an expoentail decrease of the potential
When can the potential of shear plan be measured?
during the particle movement, thus causeing the shearing off of the diffuse layer
What is the name of the measured potential?
Zeta-potential
On what does the diffusion layer depends on?
it depends on the ionic strength, higher ionic strength results to no diffsuion layer
Why is the DLVO-theory relevant?
For eletrostatic stabilization
What the born repulsion?
Occur due to small distance between the partciles(higher movemnt of the particles going above the energy barrier). it results to formation of aggregates
On what does the shape of curve depends on?
Depends stronly on the ionic strength
what happen at high ionic strength to the electrical double layer around the particles?
it causes compression of electrical double layer
What’s the advantage of the small particle size of Nanoparticles
Particles smove according to Brownian motion there negligible affected by gravity
What’s Cakeing?
no redisoersible of the sedimented particles–> inconsistent dosing
How can caking be prevented?
High viscosity of suspension, reasonable selection of stabilizer or solidification of suspension
When can the stok’es law be applied?
Just for laminar flow in cases of sedimentation
Light scattering methods for Nanoparticles?
the fraunhofer is not used, because the refractive and absorption index is needed. better Mie-theory
Dynamic light scattering measuremnet for the movement of the nanoparticles
speed of the brownian molecular movement dpending on size and vicosity
What is the attenautor?
it’s regulates the particles, more light into the curvet, less particles into the sytstem
What does high attenuator means?
higher attenuator means, less particles, desidmentation of the particle
How does the structure of a crystalline and amorphous looks like in a XRPD
crystalline shape peaks
amorphous hallo structur
How should be stability testing be perfomered?
Under trasportation and storage conditions
storage conditions
Long term, intermediate and accelerated studies
Why it is important to stabilizier nanosuspensions
because the formation of agglomeration especially for parenteral application could cuase vessel bockage and therefore embolia
What are the four scattering phenoema in light interactions with matters?
Fefraction, Reflection, Diffraction and Adsorption
which phenomenon happend with larger particles
Diffraction
Describe the diffraction phenomenon
Scattering pattern occur which is correlated with particle size
What is the angle of bigger and small particle
the smaller the particles the bigger the scattering angle
What is important if one has small particles ?
refraction and absorption become more dominating
What is then necessary using small particles
Refractive index and absorption
When can Fraunhofer theory be used
larger particles, correlation between scattering angle and particle size
Which method can be used for smaller particles
Mie-theory is used
What is Mie-theory
Modelling of scattering which results of diffraction, refraction, absorption and reflection
Which particle size can be used in laser diffraction
limited to ~ 70 nm
what can be used instead of laser diffraction
Dynamic light scattering
Dynamic light scattering
particle size
particle size measuremnets of < 1µm
XRPD
Sample is exposed to x-rays,
detector detects diffracted x-rays
Crystalline state in XRPD
Angle dependent high X-ray intensities (Bragg peaks)
Amorphous state in XRPD
No Bragg peaks detected
What is the procedure of the Dynamic light scattering
Measurement of the time-dependent fluctuations of the scattered light intensity and determine of the difusion coefficient
XRPD for which state of the molecule
Solid state
What is a power compensating DSC
Differential power signal is recorded as function of actual sample temperature
Which stability study have to be carried out for nanosupsension
Long term stability and accelarted stability Thermal stability (storage at high temperatures)
