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PH
number of grams equivalent of H per liter of solution

pH = -log [H]
pH = log 1/[H]

PHYSICAL AND CHEMICAL Quality Control 1 Lecture

Prepared by: Samantha Leigh L.
PROPERTIES OF DRUG MOLECULES Ocampo, RPh

PH STRONG ACID AND BASES

Protolysis  If an acid is introduced into an aqueous solution the [H+]
a process whereby a proton is transferred from one molecule to increases.
another.
 If the pH of an aqueous solution is known, the [H+] is
 Autoprotolysis given by the expression 10-pH
 a process whereby there is a transfer of a proton from one
molecule to another identical molecule.
 Amphoteric
 properly where a substance can act either as acid or base.

STRONG ACID AND BASES STRONG ACID AND BASES

 A strong acid is completely ionized in water and [H+] is  Calculate the pH of the following solutions:
equal to its molarity. 1. 0.05M HCl
2. 0.05M NaOH
3. 0.02M KOH

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WEAK ACID AND BASES WEAK ACID AND BASES

 Weak acids are not completely ionized in aqueous solution and Calculate the pH
are in equilibrium with the dissociated acid. 1. 0.1 M Formic acid (ka = 1.77 x10-4)
2
𝑥
Ka / Kb = 2. 0.05M Phenol (ka = 1.3 x10-10)
𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
3. 0.15M Ethylamine (kb = 5.6 x10-4)
pH(acid) = -log [H+]
pH(base) = 14 - pOH

HENDERSON- HASSELBALCH EQUATION HENDERSON- HASSELBALCH EQUATION

pH = pka + log [salt]/[acid] Calculate the pH of a soln which contains
- 3.7 x 10-2 mole of Hac
pH = pka=log [conjugate base]/[base]
- 4.8 x 10-2 mole pf Na Ac in a liter of solution pKa 9.26.

HENDERSON- HASSELBALCH EQUATION IONISATION OF DRUG MOLECULES

A buffer solution containing 0.1M each of HAc & NaAc, is present Acid:
with a Ka of HAc = 1.8 x 10-5 at 25oC. Find the pH of the −
10𝑃ℎ 𝑝𝑘𝑎
solution. %ionization = − x 100
1+10𝑃ℎ 𝑝𝑘𝑎

pH = pka + salt /acid

= [-log(1.8x10-5)] + [0.1M/0.1M] Base:
−
= 5.74 10𝑝𝑘𝑎 𝑝ℎ
%ionization = − x 100
1+10𝑝𝑘𝑎 𝑝ℎ

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IONISATION OF DRUG MOLECULES BUFFERS

Calculate the percentage of ionization of ammonia Prepared from any weak acid or base and are used to maintain the ph
of a solution.
at ph of 8.25. (pka = 9.25)
− Simplest type of buffer is composed of weak acid or base combination
10𝑝𝑘𝑎 𝑝ℎ
%ionization(base) = − x 100 with a strong base or acid.
1+10𝑝𝑘𝑎 𝑝ℎ
. − .
109 25 8 25 Common buffer system is sodium acetate/acetic acid buffer system.
= 1+109.25−8.25 x 100
Most direct way of preparing this buffer is by addition of NaOH to a
= 101 /
1+ 10 1 solution of acetic acid until the required ph is reached.
= 10 / 11 X 100 Most effective range for a buffer is 1pH; either side of the pka value of
= 90.91% the weak acid or base.

BUFFER CAPACITY ZERO ORDER DEGRDATION

 ability of a buffer solution to resist changes in pH upon addition The rate of degradation is independent of the concentration of the
of acid/alkali reactants
This type of degradation is typical of hydrolysis of drugs in
suspensions or in tablets.
Van slyke
 was responsible for a quantitative expression Different concentration , same rate
 amount in g/l of strong acid or a strong base required to be
added to a solution to change its pH by 1 unit.
 higher buffer capacity, lower change in pH.

ZERO ORDER DEGRDATION FIRST ORDER DEGRDATION

 Dependent on the concentration.
Typical in hydrolysis of a drug in a solution.
 Double rate, double concentration
 Half life(t1/2)

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FIRST ORDER DEGRDATION HALF LIFE

Double Concentration
 Calculate the half life of Procaine at 37 degrees Celsius and pH
Double Rate of 8 (k = 1.04 x 10-2 h -1)
E.g. Radioactive Decay
T1/2 = 0.693 / k
= 0.693 / 1.04x 10-2
= 66.7 h-1

STERIOCHEMISTRY OF DRUGS STERIOCHEMISTRY OF DRUGS

 Geometrical isomerism  Chirality?
-Uncommon  Enantiomers?
-Example: Zimeldine, Amitriptyline  Diasteriomers?

STERIOCHEMISTRY OF DRUGS STERIOCHEMISTRY OF DRUGS

 Chirality – is a non-superimposable on its mirror image.  Chirality and Optical
isomerism
 Enantiomers – are chiral molecules that are mirror
images of one another. -Widespread
-Usually contain one or two
 Diasteriomers - are stereoisomers that are not mirror chiral centers
images of one another and are non-superimposable on -Example: Adrenaline (exist
one another. as enantiomers, mirror
image and non
superimposable)

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STERIOCHEMISTRY OF DRUGS
 Diasteriomers
-Where more than 1 chiral center is present in a molecule.
-Example: Captopril, Labetalol

STERIOCHEMISTRY OF DRUGS