PH2107 - Solutions 2 Flashcards
What is the major problem with mixtures of polymorphs?
Differential dissolution in GI tract - dosage irregularities
different structures dissolve at different rates.
What effect does differing dissolution rates have?
- stability / shelf life
- formulation properties
- processing properties
How many forms does chloramphenicol-3-palmitate (CAPP) have?
At least three polymorphic forms and one amorphous form
Which forms of chloramphenicol-3-palmitate (CAPP) are used?
Form A - most stable and marketed
Form B - 8 fold higher bioactivity than form A
What is the problem with administering the wrong polymorph of chloramphenicol-3-palmitate (CAPP)?
Danger of fatal overdoses because of alterations in process or storage conditions
What can polymorphism be rectified by?
Heat treatment
What is the partition coefficient?
A measurement of drug lipophilicity or hydrophilicity
How is the partition coefficient measured?
solubility of x in non-aqueous medium (e.g. octanol) / solubility of x in aqueous medium (i.e. water)
What is CLogP?
A computerised LogP
What is an ionic compound?
A molecule (drug) with a formal charge
How is an acidic compound made?
By loss of an electron
How is a basic compound made?
By gaining an electron
What is a zwitterion?
A molecule or ion having separate positively and negatively charged groups.
How does the presence of a charge affect the solubility of a molecule?
A charged substance becomes
- more soluble in polar solvents (e.g. water)
- less soluble in organic solvents (e.g. hexane)
What is ionic strength?
The sum total ion concentration in solution
Why is knowing ionic strength important to chemists?
Ions have an electrical charge that attract or repel each other
What is the distribution coefficient, D and LogD?
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
How is the distribution coefficient measured?
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
What must be specified when determining D?
The pH as LogD is pH dependent
Which pH is of particular interest, and why, when determining LogD?
pH 7.4 as it is physiological pH of plasma
What is the physiological pH of the stomach?
pH 2
What is the physiological pH of the kidneys?
pH 4.2 (variable)
