P.CEUTICS2: Physical + Chemical Properties of Drugs + Excipients Flashcards
How was etoposide + doxorubicin formulation problems solved?
- Etoposide in solution containing sodium salicylate
- Doxorubicin parabens used in lyophilised formulation
What are the chemical features of etoposide which allow it to complex with salicylate salt?
Planar orientation of drug + salicylate salt improves solubility in aqueous solution
- decrease precipitation
- decrease protein binding
- enhanced bioavailability
- increase solubility leads to:
- lower volume of injection
- better formulation stability
What are the chemical features of doxorubicin which allow it to complex with benzoate esters?
Parabens (p-hydroxybenzoic acid esters) complex with Dox
- disrupts self-assembly of drug
- enables rapid dissolution of drug
- enhanced bioavailability
- more predictable dosing
What are the issues of etoposide?
- Low H20 solubility
- Can crystallise or precipitate
- Binds to plasma proteins
What are the issues with dox?
- Can form stacked dimers + polymeric self-assembly aggregates
- pi-pi interactions strong between aromatic rings
What is etoposide phosphate?
- Prodrug
- H20 soluble
- available as dry powder for dilution or preformed solution
- infused over 5 minutes to 3.5 hours
Difference between etoposide + etoposide phosphate
How is doxorubicin formulated?
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What are the molecular targets for cancer?
Describe the use of bevacizumab
Protein formulations cannot be delivered ______
What are the properties of protein?
What are the formulation demands for proteins?
Proteins are amphiphilic.
How come?
What is the half-life of bevacizumab?
How long does it take to reach steady state?
Who has a higher bevacizumab clearance?
