The basic Bronnsted definition of acids and bases are:
An acid is a species having a tendency to lose a proton.
A base is a species having a tendency to accept a proton.
pH
pH is a measure of the hydrogen ion concentration of a solution. Solutions with a high concentration of hydrogen ions
have a low pH and solutions with a low concentration of H + ions have a high pH. The equation that defines pH is
given as follows:
pH = -log [H+] concentration,
This is read:
The pH is equal to minus the log of the H+ concentration.
For example the H+ concentration is very low, let’s say about 0.0000001M, then the pH is
pH= -log[0.0000001] which is the same as -log[1 X 10-7]
The term log [1 X 10-7] = -7
- (-7) = 7
A difference of one pH unit (i.e. from pH 2 to pH 3) is a tenfold (10X) difference in H+ ion concentration.
Pure water should have a pH of 7.0
Solutions with a pH below 7.0 are termed acidic and solutions with a pH above 7.0 are termed basic.
The numerical values of hydrogen ion concentration may vary enormously; for a normal solution of a strong acid the
value is nearly 1, whereas for a normal solution of a strong base it is approximately 1 × 10 -14; there is a variation of
100,000,000,000,000 between these two limits Because of the inconvenience of dealing with such large numbers, in
1909, Sørenson proposed that hydrogen ion concentration be expressed in terms of the logrithm. It is a numeric scale
used to specify acidity or basicity of an aqueous solution. This enables the pH of a solution to be considered on a
numerical scale from 0–14 and is more convenient in terms of speech, writing and data manipulation. Acidic solutions
have pH values less than 7 whereas basic solution have pH value greater than 7 while neutral solution have pH value
equal to 7.
The pH scale is logarithmic and as a result, each whole pH value below 7 is ten times more acidic than the next higher
value. For example, pH 4 is ten times more acidic than pH 5 and 100 times (10 times 10) more acidic than pH 6. The
same holds true for pH values above 7, each of which is ten times more alkaline (another way to say basic) than the
next lower whole value. For example, pH 10 is ten times more alkaline than pH 9 and 100 times (10 times 10) more
alkaline than pH 8.
Example: If an acid has an H+ concentration of 0.0001 M, find the pH.
Solution:
First convert the number to exponential notation, find the log, then solve the pH equation.
H+ = 0.0001M = 10-4; log of 10-4 = -4;
pH = - log [ H+] = - log (10-4) = - (-4) = +4 = pH
The purpose of the negative sign in the log definition is to give a positive pH value.
pH Scale:
The pH scale, (0 - 14), is the full set of pH numbers which indicate the concentration of H+ and OH- ions in water.
pH Scale Principle:
H+ ion concentration and pH relate inversely.
OH- ion concentration and pH relate directly.
The following statements may be made about the pH scale numbers.
a. Increasing pH means the H+ ions are decreasing.
b. Decreasing pH means H+ ions are increasing.
c. Increasing pH means OH- ions are increasing
d. Decreasing pH means OH- ions are decreasing
IMPORTANCE OF pH IN PHARMACY
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 increases (to a limit) as pH increase and solubility of weak bases increase (to a limit) as pH decreases.
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. The ease of absorption of drugs from the gastrointestinal tract into the blood. For example, many (about 75%)
drugs are weak bases or their salts. These drugs dissolve more rapidly in the low pH of the acidic stomach.
However, there will be little or no absorption of the drug there as it will be too ionized. Drug
absorption normally will have to wait until the more alkaline intestine where the ionization of the dissolved
weak base is reduced
4. Body tissues (extremes of pH are injurious).
BUFFER DEFINITION
A buffer is a solution containing either a weak acid and its salt or a weak base and its salt, which is resistant to
changes in pH. In other words, a buffer is an aqueous solution of either a weak acid and its conjugate base or a weak
base and its conjugate acid.
Buffers are used to maintain a stable pH in a solution, as they can neutralize small quantities of additional acid or
base.
For a given buffer solution, there is a working pH range and a set amount of acid or base that can be neutralized
before the pH will change. The amount of acid or base that can be added to a buffer before changing its pH is called
its buffer capacity (β) or the amount of strong acid or strong base, expressed as moles of H + or OH − ion, required
to change the pH of 1 litre of the buffer by 1 pH unit.
EXAMPLES OF BUFFERS
blood - contains a bicarbonate buffer system phosphate buffer
TRIS buffer
When a buffer solution is prepared, the pH of the solution is adjusted to get it within the correct effective range.
Typically a strong acid, such as hydrochloric acid (HCl) is added to lower the pH of acidic buffers. A strong base,
such as sodium hydroxide solution (NaOH), is added to raise the pH of alkaline buffers.
Types of Buffer Solutions
Buffers are broadly divided into two types; acidic and alkaline buffer solutions. Acidic buffers are solutions that have
a pH below 7 and contain a weak acid and one of its salts. For example, a mixture of acetic acid and sodium acetate
acts as a buffer solution with a pH of about 4.75. Alkaline buffers, on the other hand, have a pH above 7 and contain a
weak base and one of its salts. For example, a mixture of ammonium chloride and ammonium hydroxide acts as a
buffer solution with a pH of about 9.25.
HOW BUFFERS WORK
A mixture of acetic acid (CH 3COOH) and sodium acetate (CH3COONa); Here, acetic acid is weakly ionized while
sodium acetate is almost completely ionized. The equations are given as follows:
CH3COOH ⇆H+ + CH3COO-
CH3COONa ⇆ Na+ + CH3COC-
To this, if you add a drop of a strong acid like HCl, the H + ions from HCl combine
with CH3COO- to give feebly ionized CH3COOH. Thus, there is a very slight change in the pH value.
CH3COO- + H+ ⇆ CH3COOH
Now, if you add a drop of NaOH, the OH- ions react with the free acid to give undissociated water molecules.
CH3COOH + OH- ⇆ CH3 COO- + H2O
In this way, the OH- ions of NaOH are removed and the pH is almost unaltered.
UNIVERSAL BUFFERS
Most buffers work over a relative narrow pH range. An exception is citric acid because it has three pKa values. When
a compound has multiple pKa values, a larger pH range becomes available for a buffer. It's also possible to combine
buffers, providing their pKa values are close (differing by 2 or less), and adjusting the pH with strong base or acid to
reach the required range. For example, McIvaine's buffer is prepared by combining mixtures of Na 2PO4 and citric
acid. Depending on the ratio between the compounds, the buffer may be effective from pH 3.0 to 8.0.
A mixture of citric acid, boric acid, monopotassium phosphate, and diethyl barbituic acid can cover the pH range from
2.6 to 12.
Applications of Buffers
1. In biological systems:
The pH of blood is maintained at about 7.4 by two buffer systems. That are;
a) primary buffers: these are present in plasma. The plasma contains; carbonic acid / carbonate & acid /alkali
sodium salt of phosphoric acid.
b) secondary buffers: these are present in erythrocytes which are; oxy-haemoglobin /haemoglobin & acid /
alkali potassium salts of phosphoric acid.
2. In pharmaceutical systems:
Buffers are widely used in the field of pharmacy as ingredients in most of the pharmaceutical formulations in
order to adjust the pH of the product to that required for maximum stability.
In parenteral preparations (i.e. injections):
In case of parenteral preparations, pH should be considered carefully as large deviations of pH may lead to
serious consequences. The ideal pH of a parenteral product is 7.4, which is pH of blood. The most commonly
used buffers in parenteral products (injections) are acetate, phosphate, citrate and glutamate.
In ophthalmic preparations (i.e. eye preparations):
Buffers are generally used in ophthalmic preparations to maintain the pH within the physiological pH range
of lacrimal fluid (i.e. eye fluid). The lacrimal fluid has a pH in rang 7 – 8, but it has good buffering capacity
and can tolerate preparations having pH values between 3.5 –10.5 with little discomfort. Outside this range
(i.e. 3.5 – 10.5), increase lacrimation may occur with other complications.
The buffering agents most commonly used in ophthalmic preparations include borate, carbonate and
phosphates.
In ointments and creams:
Topical products (which are used on skins) such as ointments and creams are also buffered to ensure stability
of the formulation. The most commonly used buffers in ointments and creams are citric acid / its salts &
phosphoric acid / its salts.
3. Buffer solutions are necessary to keep the correct pH for enzymes in many organisms to work. Many enzymes
work only under very precise conditions; if the pH moves outside of a narrow range, the enzymes slow or stop
working and can denature. A buffer of carbonic acid (H 2CO3) and bicarbonate (HCO−3) is present in blood
plasma, maintaining a pH between 7.35 and 7.45.
4. Industrially, buffer solutions are used in fermentation processes and in setting the correct conditions for dyes
used in colouring fabrics. They are also used in chemical analysis and calibration of pH meters.
5. The majority of biological samples that are used in research are made in buffers, especially phosphate buffered
saline (PBS) at pH 7.4.
Tonicity
Tonicity is the concentration of a solution as compared to another solution. Concentration describes the amount of
solutes dissolved by a solution. If a solution has a higher concentration of solutes (less water) than another it is said to
be hypertonic. A hypotonic solution has a lower concentration of solutes and more water than another
solution. Isotonic solutions contain the same concentration of solutes. In biology, the tonicity of the environment
compared to the cell determines how water moves across the semipermeable membrane. The graphic below shows the
tonicity of different environment, and which way water moves. Remember, water moves to balance the concentration
gradient of the solutes. It will move from high solute concentration to low solute concentration.
Hypotonic – When one solution contains more water and less solutes than another solution.
Hypertonic – A solution of higher concentration that the solution it is being compared to.
Isotonic – Two solutions that exist with the same solute concentration.
Osmolarity – The concentration of a solution in parts of solute divided by volume of water.