L22, 23, 24, 25, 26, 27 Solutions Flashcards
(87 cards)
22
What Is Preformulation?
Definition:
Preformulation involves studying a drug’s physicochemical and biopharmaceutical properties to guide formulation design.
Importance:
Predicts formulation challenges
Informs dosage form design (e.g., solution, suspension, tablet)
Influences solubility, stability, bioavailability
22
What are crystallinity and polymorphism, and how do they affect formulation?
Crystallinity refers to whether a drug has a defined crystal lattice.
Polymorphism refers to different crystal forms of the same drug.
Both influence solubility and bioavailability. Stronger lattices reduce solubility, affecting dosage form design (e.g. need for co-solvents in solutions or disintegration/dissolution issues in tablets).
22
Why are particle size and shape important in formulation?
They control dissolution rate and powder flow, both crucial for selecting the dosage form (solution, suspension, tablet). Small or irregular particles may dissolve slowly or flow poorly in manufacturing, affecting bioavailability and processability.
22
What is hygroscopicity and how does it influence formulation?
Hygroscopicity is the ability of a solid to absorb moisture from the air. Moisture uptake can degrade drugs and hinder powder flow. It influences formulation choices (e.g. riskier in granules/tablets), and may require protective packaging like blister packs.
22
What is the difference between solubility and dissolution, and why are they important?
Solubility: Maximum amount of solute that can dissolve at equilibrium
Dissolution: The rate at which solute dissolves (a kinetic process)
Both affect bioavailability. Poor solubility or slow dissolution limits absorption. High values may cause rapid onset and toxicity.
22
How do pKa and pH affect drug solubility and absorption?
Ionised drugs: more soluble but less permeable
Unionised drugs: better absorbed
Formulations may use buffers or pH modifiers. Site of absorption (stomach vs intestine) may require techniques like enteric coating.
22
What is the partition coefficient (Log P) and how does it affect drug formulation?
Log P indicates a drug’s lipophilicity (hydrophilic vs hydrophobic). It affects solubility, absorption, and bioavailability across all dosage forms. Poorly balanced Log P may require formulation strategies to optimise solubility and permeability.
22
What stability issues must be considered in formulation?
Drugs may degrade via hydrolysis, oxidation, photolysis, or racemisation. Solutions are less stable; tablets more stable. Formulation strategies include:
- pH optimisation
- Light protection (e.g. amber bottles)
- Cold storage
- Reconstitution at point of use (e.g. cisplatin)
22
What are the key biopharmaceutical properties influencing oral bioavailability?
Solubility in GI fluids
Permeability across intestinal mucosa
High bioavailability requires a good balance of both. The Maximum Absorbable Dose (MAD) depends on solubility, absorption rate, SIWW (250 mL), and SITT (270 minutes).
22
What is a pharmaceutical solution and what must be considered when formulating one?
A pharmaceutical solution is a homogenous molecular mixture of solute(s) in a solvent.
Key formulation considerations include:
Solvent choice
Solubility and dissolution rate
Stability
Patient acceptability (e.g. taste)
Dosing precision
22
What are common formulation strategies for poorly soluble drugs in solution?
To enhance solubility:
Use co-solvents (e.g. ethanol, propylene glycol)
Adjust pH to favour ionised form
Add surfactants to reduce surface tension
Use complexation agents (e.g. cyclodextrins)
These strategies improve solubility, stability, and patient compliance (e.g. taste masking).
22
What are the types of pharmaceutical solutions?
Types include:
Aqueous solutions (water-based)
Syrups (sugar-based)
Elixirs (alcohol-based)
Tinctures (high alcohol concentration)
Spirits, Aromatic waters, Glycerins
Each type varies in solvent, use, and drug compatibility.
22
How is the choice of solvent important in solution formulation?
Solvent must:
Be pharmaceutically acceptable and safe
Dissolve drug and excipients effectively
Ensure chemical stability
Match the route of administration (e.g. alcohol not for paediatrics)
Common solvents: water, ethanol, propylene glycol, PEGs
22
Why is dissolution testing important in pharmaceutical development?
Dissolution testing:
Predicts in vivo performance (bioavailability)
Assesses batch-to-batch consistency
Ensures drug release profile matches design (e.g. immediate or modified release)
Is a regulatory requirement for quality control
23
What is dissolution and why is it important in pharmaceutical formulation?
Dissolution is the transfer of molecules or ions from the solid state into solution. It is essential because it governs the rate and extent of drug absorption, especially for oral dosage forms, and influences bioavailability and onset of action.
23
What happens during the dissolution process at the molecular level?
The solid drug interacts with the solvent. Initially, molecules detach from the solid and enter a boundary layer at the solid–solvent interface. Then, they diffuse through the boundary layer into the bulk solution. Diffusion is the rate-determining step because it is the slowest.
23
What is the heat of mixing (ΔE), and how does it relate to ideal and non-ideal solutions?
ΔE = 0: Ideal solution (cohesive forces = adhesive forces)
ΔE > 0: Endothermic (energy needed; less spontaneous)
ΔE < 0: Exothermic (energy released; more spontaneous)
In non-ideal solutions, cohesive ≠ adhesive forces, affecting solubility and mixing behaviour.
23
What are sink conditions and why are they important?
Sink conditions occur when the solvent can dissolve 5–10× more drug than the dose being administered. This keeps the concentration gradient high and drives dissolution forward.
If C ≥ Cs, dissolution stops as the solution becomes saturated.
In vivo, sink conditions occur when absorption > dissolution rate.
23
What is the Noyes–Whitney equation and what variables affect it?
dC/dt = (D x A x (Cs-C))/h
D = Diffusion coefficient
A = Area of solute
Cs = Saturation concentration
C = Drug concentration in bulk
h = Thickness of diffusion layer
As C increases, (Cs-C) decreases, meaning slower dissolution rate
23
What is the Intrinsic Dissolution Rate (IDR) and why is it measured?
IDR is the rate of dissolution of a pure drug when variables like surface area, agitation, pH, and ionic strength are held constant.
It gives a standardised measure of how quickly a drug dissolves, used to:
Compare batch-to-batch equivalency
Screen new drug candidates
Understand drug solution behaviour
23
How is the Intrinsic Dissolution Rate (IDR) measured in practice?
Using the Static Disc Method:
Drug is compressed into a disc of known surface area
Placed in dissolution fluid at 37°C
Rotating paddle (100 rpm) stirs the solution
This setup isolates the drug’s dissolution performance.
23
What is the Hixson–Crowell Cube Root Law and when is it used?
This law models the dissolution of powders where surface area decreases as dissolution occurs.
It relates the cube root of the undissolved mass (M¹ᐟ³) to time, yielding a linear plot:
(M0¹ᐟ³) - (Mt¹ᐟ³) = kt
k = dissolution rate constant (not the same as intrinsic k)
24
Why is pKa important in pharmaceutical formulation?
pKa reflects the dissociation tendency of weak acids or bases and helps predict how ionised or unionised a drug will be at a given pH.
This affects:
Solubility (ionised = more soluble)
Absorption (unionised = better absorbed)
It is especially relevant for oral and IV drug delivery.
24
What is the relationship between acids, bases, and pH in terms of solubility?
Weak acids are more soluble in alkaline (high pH) solutions
Weak bases are more soluble in acidic (low pH) solutions
This is due to greater ionisation in opposite pH environments. Ionised forms dissolve better, while unionised forms cross membranes more easily.
