RE lecture 1 Flashcards
How is onset/release of a drug controlled?
- rapid onset: use injections or inhalation
- for prolonged onset: use extended release tablets
- for targeted release: nanomedicines
How are medicines protected from the gastric environment of the stomach?
Enteric coated tablets
How are drugs delivered if they want to bypass first pass metabolism?
Drugs that don’t pass through the GI tract eg: injections, creams, sublingual etc
How to improve patient’s acceptance to the drug?
- mask undesirable odour
- mask undesirable taste
What happens before preformulation?
primary characterisation of drug and excipients
Why are preformulation studies important?
- Learn about the physical and chemical properties of the candidate drug and excipients
- This allows for quick remediation action when a problem arises
- ensures the quality of the drug
What is polymorphism?
Change in physical state of the drug, but not the chemical state
What is the drawback of a drug being insoluble in water?
- Poor dissolution in the GI tract–> less absorption into the bloodstream—> low bioavailability
- hard to develop medicines that can be administered non-orally
What are parenteral formulations?
Dosage forms that are administered non-orally.
What are the differences between crystalline and amorphous states?
- Crystalline forms have a definite ordered internal structure while amorphous forms have no fixed internal structures
- Crystalline forms are more stable that amorphous forms as they have lower internal energy.
- Crystalline forms are less soluble than amorphous forms.
- Crystalline forms have less inclination to change its from during storage than amorphous forms.
What are the different types of API solid states?
- amorphous
- form 1
- form 2
- solvates/hydrates
- salts
- cocrystals
What are polymorphs?
Crystalline forms with the same chemical composition but different internal structures (packing, conformation, etc)
Define preformulation.
Primary characterisation of a drug and excipients for certain fundamental physical and chemical properties.
What does it mean for a drug to be hygroscopic?
It absorbs moisture from the air
What are the commonly evaluated physical parameters during preformulation?
- Solubility and permeability
- BCS classification
- Solid state properties
- Polymorph screen
- Salt screen
- Amorphous solid dispersion screen.
Why is it important that a drug be soluble in water?
The drug must be in solution to be absorbed.
What is the biopharmaceutical classification system?
A scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability.
When is a drug considered as highly soluble?
When its highest dose strength is soluble in about 250ml of water over a pH range on 1 to 7.5
When is a drug considered to be highly permeable?
When the extent of absorption in humans is determined to be more than 90% of an administered dose, based on mass balance or in comparison to an IV reference dose
What are the different BCS classifications and what do they mean?
- BCS class I: high solubility and permeability
- BCS class II: low solubility and high permeability
3.BCS class III: high solubility and low permeability - BCS class I: low solubility and permeability
What is the function of polymorph screening?
Assess all the polymorph structures to select the most thermodynamically stable form
Are hygroscopic substances desirable as drugs?
No
What is the function of salt screening?
To make a salt form of the API so that it can be more soluble in water.
Salt forms may also improve melting point and stability
Why do BCS class I compounds not need salt screening
Because the compound is already very soluble in water.
Why is it important that the API doesn’t exhibit complex polymorphic behaviour?
If the drug polymorph changes during storage or transport, it could affect solubility and stability
When is amorphous solid dispersion screening done?
When the other methods of screening do not produce a soluble compound
What is done during ASD screening?
The API is mixed with a polymer and sometimes a surfactant
Why is a polymer used to make ASD?
The polymer stabilises the amorphous state of the API in the solid form to prevent recrystallisation during dissolution.
ASD’s are normally formulated as what dosage form?
Tablets
What is thermodynamic and kinetic solubility?
- Thermodynamic solubility measures to what extent a solute dissolves
- Kinetic solubility measures to what extent the solute precipitates
Is thermodynamic or kinetic solubility the gold standard for solubility?
Thermodynamic solubilty
F
