part 3 flashcards of key bits besides stuff on ppt

What is the primary scientific definition of solubility?

The extent to which dissolution proceeds under a given set of experimental conditions.

How is solubility alternatively defined in terms of equilibrium? 

The amount of a substance that passes into solution when equilibrium is established between the solution and excess (undissolved) substance, forming a saturated solution. 

What is another alternative definition for solubility regarding volume? 

The capacity for solute in a given volume of a solvent. 

How is solubility typically expressed and what are the four most commonly seen expressions? 

Expressed as the maximum concentration possible in a given set of conditions. See ppt for examples

definition of miscibility?

Two components forming a solution where they are either both gases or both liquids

What’s a saturated solution and what happens to any further added solute

Solution in which no more solvent molecules are available to form solvation shells, any further added solute will remain undissolved

What indicates saturated solution

Again, If you add any further solute it won’t dissolve

Solubility vs dissolution

Amount vs rate

True or False: If a solute is very soluble in a solvent, it must also have a high dissolution rate?

False. It is possible for a solute to be very soluble yet dissolve slowly (i.e., a low dissolution rate), and vice-versa.

What two key parameters must be defined before measuring solubility? 

Solvent and temp conditions e.g. water at 20 degrees

How is a saturated solution initially made when measuring solubility? (Step 1)

Pure solute is added to pure solvent using either a long mixing time or heating followed by cooling. 

What laboratory technique is used to separate any undissolved solute from the solution? (Step 2)

Centrifugation

What is collected after centrifugation, and what is it defined as? (Step 3)

Supernatant - clear liquid layer remaining above the solid residue after centrifugation. 

What analytical methods can be performed on the supernatant to determine the amount of dissolved solute present? (Step 4)

Techniques such as HPLC (High-Performance Liquid Chromatography) or UV spectrometry. 

Why are replicates performed during the solubility measurement process?  (Step 5)

To determine accurate value

What primary aspect of a drug molecule determines its polarity and subsequently affects its solubility?

Its molecular structure, in particular its functional groups. 

How can an R group be modified to make a drug more soluble (more polar)?

By introducing elements or groups containing oxygen, sulfur, or nitrogen (O/S/N). (Ensure biological func of drug isn’t affected)

Order the following functional groups from lowest to highest polarity: Methoxy (OCH_3), Carboxylic acid (COOH), Methyl (CH_3), and Alcohol (CH_2OH). 

1. Methyl (CH_3) — Lowest polarity 

2. Methoxy (OCH_3) 

3. Alcohol (CH_2OH) 

4. Carboxylic acid (COOH) — Highest polarity

What is the formula and definition for the partition coefficient (P_{octanol/water}) of a substance?

(Use formula as definition)

What does the logarithm of the partition coefficient (\log P_{octanol/water}) measure?

provides a convenient measure of how lipophilic or hydrophilic a drug molecule is.

How do you interpret large negative values, large positive values, and values close to 0 on the \log P scale? 

See slide

What structural characteristic directly influences the \log P value of a drug?

The \log P of a drug depends on its ionisation state.

How does the polarity and lipophilicity/hydrophilicity of an ionised drug molecule compare to its un-ionised form?

An ionised drug molecule is more polar and hydrophilic, whereas the un-ionised form (such as a free acid like -{COOH} or free base) has low polarity and is lipophilic. 

What is the practical use of inducing ionisation in drug molecules? 

It can be used to tailor polarity.

Can ionised drugs exist in isolation, and what is formed when they combine with a counterion?

No, ionised drugs cannot exist in isolation; they require a counterion, forming a Drug Salt (\text{Drug} + \text{Counterion} = \text{Drug Salt}).

What determines whether a drug should be used as a free base (or acid) versus a salt? 

Route of administration

Why is the ionic state of a drug manipulated during formulation?

It is manipulated to suit the specific route of administration. 

Why is lidocaine hydrochloride salt suitable for injectable dosage forms? 

It is hydrophilic and water-soluble, providing a polar form suited for polar/aqueous environments such as the bloodstream.

Why is lidocaine hydrochloride salt suitable for injectable dosage forms? 

It is hydrophilic and water-soluble, providing a polar form suited for polar/aqueous environments such as the bloodstream.

What properties of a molecule are influenced by the counter ion?(2)

Stability and solubility

What properties of a molecule are influenced by the counter ion?(2)

Stability and solubility

Do counterions possess any pharmacological action?

No, the counterion has no pharmacological action, but it can significantly affect the physical and chemical properties of the drug.

What four key factors can be influenced by the choice of counterion? (So it must be carefully chosen due to its effects) (4)

1. Ion pair association constant (must not be too strong: when a drug salt is put into the body, it needs to break apart into free ions (the active drug separated from its counterion) so it can interact with its target receptors.)

If the bond between the drug and the counterion is too strong, they will stick together too tightly as an "ion pair". 

If they don't separate easily, the drug won't dissolve properly or be released into the body to do its job.

2. Toxicity levels of the counterion within the formulation. 

3. Interactions with excipients or packaging (e.g., chloride ions ({Cl}^-) can be corrosive). 

4. Acid lability, meaning the drug might be unstable to the specific acid used to make the salt (e.g., unstable to hydrochloric acid, but stable to acetic acid). 

LogP vs LogD

•LogP is the lipophilicity of compounds in the neutral form

LogD measures the lipophilicity of compounds in ionised or unionised form at a specific pH

What effect does the pH of a solution have on a drug? 

The pH of a solution will affect the ionisation state of a drug (and therefore its solubility in a given solvent)