Drug delivery Flashcards
Give at least 3 examples of how nanotechnology can improve drug delivery.
Targeting
Encapsulation, prevent degradation
Reduced dosage
Reduced systemic effects
Why do you think poor solubility of drugs problematic? Give at least 2 reasons
Cannot reach the target in the end
Varied results depending on eating
Lack of dosage proportionality
What is Lipinski’s rule of five? Describe key concepts in your own words
Generally no more than one violation of:
Molecular weight < 500 Da
logP value < 5
Hydrogen bond donor <5
Hydrogen bond acceptor <10
What is LaMer’s theory of nucleation and crystal growth?
Three regions:
1: Concentration increase with nucleation
2: Supersaturated state > nucleation start (burst nucleation phase)
3: Crystal growth, aka particles add on to nuclei > slower in the end due to less freely monomers (diffusion controlled)
Can you describe the state of supersaturation in the context of drug solubility? Make connection to nanotechnology context
We want drug in supersaturated state – as much as possible but in amorphous state
Based on LaMer’s theory of nucleation and crystal growth, suggest a synthesis route that can achieve homogeneous and controlled particle size. Describe its fundamental principle
Constant monomer supply, controlled particle size
Monodisperse
What does the Ostwald-Freundlich relationship say?
Size and solubility are connected.
Smaller particles are more soluble. However, nanoscale after a critical point is the opposite – electrostatic interactions increase with too small, and solubility decrease with size
What is Ostwald ripening?
Larger particles become larger, smaller become smaller when crystal growth
What would be the benefit of using nanosuspensions compared to conventional drugs? Give 5
- Higher bioavailability
- Less reliant on food intake
- Increased rate of absorption
- Increased absorption of higher dosage
- Rapid formulation development
Can you give at least one example of nanosuspension/nanocrystal product approved for clinical use? Elaborate
Doxa for breast cancer.
Its properties and benefits are:
* Released from carrier enzymatically
* Higher accumulation in tumor cells
* Increased circulation size
* Reduction of cardio-toxicity
What would be necessary to ensure the stability and clinical use of nanosuspensions/nanocrystals?
Prevent agglomeration e.g. with surfactants (might have their own effect, steric hinderance?, changed surface chemistry?)
Work in the body – no harm, no elimination (PEG etc.)
What are typical properties of amorphous solids?
No repetitive structure of more than 10 repeating units
No peaks in XRD
No melting point (not the same)
What size of pores what be more suitable to obtain stable amorphization through melting point depression?
Mesopores 2-50 nm
Which cells are capable of enhancing the permeability of NPs from gastrointestinal tract?
M-cells, lymphatic cells in the GIT
Give at least two examples of nanotechnology related strategies to achieve enhanced solubility/bioavailability for poorly soluble drugs
Nanocarrier – put in amorphous state, prevent recrystallization with crystal carrier
Decrease size – nanosuspensions
