Unit 2 Physical Pharmacy
Unit 2 Physical Pharmacy
Unit 2 Physical Pharmacy
applications, indicators
Søren Peter Lauritz Sørensen (9 January 1868 – 12 February 1939) was a Danish chemist,
famous for the introduction of the concept of pH, a scale for measuring acidity and
alkalinity.
Sørensen's scale assigns a pH of 1 to 14, with 1 being the most acidic, 14 being the most
basic, and 7 being neutral (neither acidic or basic). The pH scale works in powers of ten,
so each jump in number is a multiple of 10 in concentration.
pH stands for 'potential of Hydrogen' which measures the acidity or alkalinity of water-
soluble substances.
The pH value of any solution is numerically equal to the logarithm of the inverse of the
hydrogen ion (H+) concentration. Hence, the pH solution is referred to as the negative
logarithm of hydrogen ion.
pH = -log [H+]
= log 1/ [H+]
IMPORTANCE Of pH IN PHARMACY
It is most important to determine suitable pH for a given drug in solution at early stages of
drug discovery. If the drug is to be administered as a solution dosage form then the pH of the
solution should be chosen carefully. Solution dosage forms include eye drops, nasal drops,
ear drops, oral solutions, injectable...etc.
The following is a list of considerations to be taken while choosing a suitable pH for a drug
solution:
1. Solubility of the drug. If the drug is a weak acid or a weak base then the pH of the
solution affects its solubility. solubility of weak acids increase (to a limit) as pH increase and
solubility of weak bases increase (to a limit) as pH decrease.
2. Stability of the drug. The pH of the solution can affect the degradation rate of the drug.
Depending on the drug, a pH at which the drug is most stable can vary. For example, aspirin
is most stable (has lowest degradation rate) at pH = 2.5.
3. Permeability of the drug through biological membranes. This depends on the extent of
ionization of the drug. The pH of the solution can affect the extent of ionization of weakly
acidic or weakly basic drugs. A Drug in the non-ionized form is more permeable than in its
ionized form.
4. Tissue irritation. The pH of a pharmaceutical solution cannot be too acidic or too basic.
The further away we get from the physiological pH (7.4) the greater the irritation. For oral
solutions the acceptable pH range can be larger than that for eye drops or injectable
solutions given the delicacy of the tissues coming in touch with the solution.
EQUATIONS OF pH
pH = -log[H+]
pOH = -log[OH-]
pKa = -log(Ka)
pKb = -log(Kb)
pKw = -log(Kw)
This logarithmic term simplifies the expression of small numbers for example if [H+] =
0.00001 moles/litre then pH = 5. If [OH-] = 5.6 × 10-8 moles/ litre then pOH = 7.25. If Ka =
1.76 × 10-5 then it is easier to express it as pKa = 4.76. Similarly if Kb = 1.6 × 10-6 then pKb
= 5.80. For water Kw = 1 × 10-14 and pKw = 14.
The terms [H+], [OH-], Ka, Kb, and Kw can be calculated from their corresponding p values
as the following:
[H+] = 10-pH
[OH-] = 10-pOH
Ka = 10-pKa
Kb = 10-pKb
Kw = 10-pKw
Relations between pH, pOH, pKa, pKb, and pKw
In a previous post the terms pH, pOH, pKa, pKb, and pKw were defined. Additionally, there
is a relation between pH and pOH and a relation between pKa and pKb which are
summarized by the following equations:
- Equations 2 or 4: can be applied on a weak acid and its conjugate base (e.g. acetic acid
and sodium acetate) or on a base and its conjugate acid (e.g. ammonia and ammonium
chloride). Thus, we can use equations 2 or 4 to find pKb (or Kb) for the conjugate base of the
weak acid and we can find pKa (or Ka) of the conjugate acid of the weak base.
For example, pKa for acetic acid is equal to 4.76 so pKb of sodium acetate is calculated as
the following:
4.76 + pKb = 14.00
pKb = 9.24
Kb = 5.75 × 10-10
Limitations of pH Scale
1. pH values does not reflect directly the relative strength of acid or bases. A solution of
pH = 1 has a hydrogen ion concentration 100 times that of a solution of pH = 3 (not three
times). A 4 x 10-5 N HCI is twice concentrated of a 2 x 10-5 N HCI solution, but the pH
values of these solutions are 4.40 and 4.70 (not double).
2. pH value is zero for 1N solution of strong acid. Concentration of 2 N, 3 N, 10 N, etc.
gives negative pH values..
3. A solution of an acid having very low concentration, say 10-8 N, shows a pH 8 and
hence should be basic, but actual pH value is less than 7.
pK value: p stands for negative logarithm. Just as and ion concentrations range
over many negative powers of 10, it is convenient to express them as pH or pOH, the
dissociation constant (K) values also range over many negative powers of 10 and it is
convenient to write them as pK. Thus, pK is the negative logarithm of dissociation constant.
and
Weak acids have higher values. Similarly weak bases have higher values
For any conjugate acid-base pair in aqueous solution,
(at 298o K)
Calculation of the pH of &
If we use the relation we get equal to 8, but this is not correct because an
acidic solution connot have greater than 7. In this condition concentration of water
cannot be neglected.
Therefore,
Since is strong acid and completely ionised,
,