PH2107 - Solutions 2

Question 1

What is the major problem with mixtures of polymorphs?

Answer 1

Differential dissolution in GI tract - dosage irregularities

different structures dissolve at different rates.

Question 2

What effect does differing dissolution rates have?

Answer 2

• stability / shelf life
• formulation properties
• processing properties

Question 3

How many forms does chloramphenicol-3-palmitate (CAPP) have?

Answer 3

At least three polymorphic forms and one amorphous form

Question 4

Which forms of chloramphenicol-3-palmitate (CAPP) are used?

Answer 4

Form A - most stable and marketed

Form B - 8 fold higher bioactivity than form A

Question 5

What is the problem with administering the wrong polymorph of chloramphenicol-3-palmitate (CAPP)?

Answer 5

Danger of fatal overdoses because of alterations in process or storage conditions

Question 6

What can polymorphism be rectified by?

Answer 6

Heat treatment

Question 7

What is the partition coefficient?

Answer 7

A measurement of drug lipophilicity or hydrophilicity

Question 8

How is the partition coefficient measured?

Answer 8

solubility of x in non-aqueous medium (e.g. octanol) / solubility of x in aqueous medium (i.e. water)

Question 9

What is CLogP?

Answer 9

A computerised LogP

Question 10

What is an ionic compound?

Answer 10

A molecule (drug) with a formal charge

Question 11

How is an acidic compound made?

Answer 11

By loss of an electron

Question 12

How is a basic compound made?

Answer 12

By gaining an electron

Question 13

What is a zwitterion?

Answer 13

A molecule or ion having separate positively and negatively charged groups.

Question 14

How does the presence of a charge affect the solubility of a molecule?

Answer 14

A charged substance becomes

• more soluble in polar solvents (e.g. water)
• less soluble in organic solvents (e.g. hexane)

Question 15

What is ionic strength?

Answer 15

The sum total ion concentration in solution

Question 16

Why is knowing ionic strength important to chemists?

Answer 16

Ions have an electrical charge that attract or repel each other

Question 17

What is the distribution coefficient, D and LogD?

Answer 17

The ratio of the sum of the concentrations of all forms of the compound (ionised plus unionised) in each of the two phases

concentration in solvent 2 / concentration in solvent 1

Question 18

How is the distribution coefficient measured?

Answer 18

The pH of the aqueous phase is buffered to a specific value, such that the pH Is not significantly perturbed by the introduction of the compound

D is given by the log of the ratio of the sum of concentration of the solute’s forms in one solvent, to that in the other solvent

Question 19

What must be specified when determining D?

Answer 19

The pH as LogD is pH dependent

Question 20

Which pH is of particular interest, and why, when determining LogD?

Answer 20

pH 7.4 as it is physiological pH of plasma

Question 21

What is the physiological pH of the stomach?

Answer 21

pH 2

Question 22

What is the physiological pH of the kidneys?

Answer 22

pH 4.2 (variable)