BASES AND ACIDS OF CHOICE

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 Bases of Choice
• Bases frequently used in pharmaceutical practice
1. CO32-
2. Hydroxide
3. HCO3- (bicarbonate)
  
• Usually used in the form of their sodium salts
• Potassium salt can be used as well but often rare. Na + is
preferred because of its physiological compatibility
• It’s the major cation in the ECF and important in impulse
transmission and maintenance of osmotic pressure
• Solubility of Na+ is almost free from acid and base properties
• Na+ + H2O NaOH + H+

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1. NaOH
• Available commercially in the from of crystals, pellets, tabs, flakes
• The compound is extremely deliquescent on exposure to air becomes
liquid and also absorbs CO2
• As a result, the solid and all solutions (except concentrates) are
contaminated to same degree with Na2CO3
• NaOH thus should always be stored in tightly sealed containers

To prepare NaOH free from contamination

a. Prepare Conc sol of NaOH (>50%). Na2CO3 will be insoluble in this sol
b. Prepare NaOH in ethanol . (Na2CO3 will be insoluble – not polar)
•  
• Since there is no accurate knowledge of amount of absorbed (Moisture +
CO2) in a given sample, simple weighing techniques are unsuitable for
measurement in Stoichiometric equations. The accurate measurement of
the compound is by use of a standard solution

HCI + NaOH NaCI + H2O

• M1V1= M2V2
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• double indicator system can be used to estimate the
amount of Na2CO3 (as impurity) in a given sample of NaOH
• The titre of the NaOH solution depends upon the indicator
used to determine end point of standardization

Indicator pH range Acid Base

Phenolphthalein 8.3 – 10.4 Colorless Red
Methyl Orange 3.1 – 4.4 Pink Colorless

Acid (Burette)
The base is titrated using a
standard acid
Base (conical flask)

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• The following are the reactions taking place.
OH- + H3O+ 2H2O
CO3 2- + H3O+ HCO3- + H2O
End point 1: phenolphthalein indicator turns colorless. (all OH neutralized. Half of carbonate
neutralized.)
Add methyl orange indicator and continue titrating till end point. (solution turns pink)
Reaction taking place is as follows:

HCO3- + H3O+ H2CO3 + H2O

• Volume used in the phenolphthalein titration (titration 1) is noted.

• New volume in the second titration is also noted.

 New volume = ½ conc. of carbonate

 New volume * 2 = vol. of titration of carbonate.

 Standard solutions are hence preferred in establishing accurate concentrations of NaOH

solutions

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Note
• Extreme care should be exercised during
neutralization of NaOH in a procedural step in
preparation of pharmaceutical solution
• Any excess of this reagent is intolerable regardless of
mode of use of preparation i.e. oral or parenteral
• A solution having excess NaOH will cause undesirable
effect ranging from irritation to corrosion
• As a very strong base, NaOH has advantage of being
able to neutralize almost all acids commonly used in
pharmacy (weak or strong)

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 NaHCO3 (baking Soda)
• Is a weak base
• Has limited value for neutralization especially strong and
moderately strong acids
• NaHCO3 presents no serious storage and handling problems.
Reasons:
1. Not sensitive to moisture and CO2
2. Obtained in sufficient purity thus direct weighing possible
(No standardization required)
• HCO3- - is heat labile for this reason heat sterilization should
be carried out in special conditions when HCO3- is present in
injectables.

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• NaHCO3 cannot be stored in areas exposed to excessive
heat – will break to CO2 + H2O 
2HCO3- CO32- + H2CO3
H2CO3 H2O + CO2 
• Solution of NaHCO3 when boiled can undergo thermal
decomposition

Use of bicarbonate injection

• Electrolyte replenishes (lost Na+ Ions )
• Systemic alkalizer
• Metabolic acidosis (diabetes ,DKA &renal failure)
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 Sodium Carbonate
• It has basic properties intermediate between
hydroxide and the bicarbonate
• Exist as anhydrous or hydrated forms. Three
hydrated forms exist
1. Decahydrate
• Crystallizes from aq. Solution at temp below 320C.
The salt is efflorescent (loss water) and it changes to
monohydrate on exposure to air (Na2CO3. H2O)
• Decahydrate form is of little use because 63% of its
content is mainly water (Na 23, C 12, O 16)
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2. Heptahydrate : crystallizes from solution at temp of 32 – 35.4 0c
3. Monohydrate:
• Crystallizers at 400c - 1090c-
• Because of its comparative stability to moisture, the monohydrate is
normally selected for use in pharmaceutical and chemical industries
• However it slowly absorbs CO2 and moisture to cause caking

• CO2 2- + H2O + CO2 2HCO3-

• Alkaline solution becomes strongly alkaline
CO32- + H2O HCO3- +OH-
HCO3- + H2O H2CO3 + OH-

• CO32- is useful agent for neutralization of wide range of acids

• Because of its stability and purity Na 2CO3 . H2O (Monohydrate) like NaHCO3
may be measured by direct weighing
• But like NaOH it has strong basic properties thus excess must be avoided.
Excess will cause – irritation
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ACIDS OF CHOICE

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• Mainly

1.HCl
2.Sulphuric Acid
3.Metaphosphoric Acid
4.Sodium Dihydrogen Phosphate
5.Organic Acids (citric acid, acetic acid, tartaric
acid)

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1. HCl
• Is usually the acid of choice for pharmaceutical
neutralization procedures because of the
physiological inertness of CI-
• The disadvantages of this acid are almost similar
to those encountered for NaOH
• Excess must be avoided. Standard solution must
be prepared. The volatility of the HCI molecule
can lead to loss of active component, can cause
small decrease in the titre especially if it is
stored in improperly stoppered bottle
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2. H2SO4
• It is suitable for both analytical and synthetic
neutralization procedures
• However for injectables and substances
intended for oral use, the accompanying SO4-
may be objectionable if in high concentration
• Due to laxative effect (stimulation of bowel
movement) may worsen diarrhea
• Mg sulphate (epsom salt) used as laxative

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3. HPO3 – Metaphosphoric acid
• Is a weak acid
• Its neutralization action is unsatisfactory to
some weaker bases. Will not give complete
neutralization
• However, it is sometimes used in
neutralization when the resultant solution is a
salt that is to be used as medical

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 Sodium dihydrogen phosphate
(NaHPO4)
• Is a suitable crystalline acid for neutralization
of strong bases mainly.
• It is generally suitable for preparation of
solutions by weight method because it is
stable
• Approximate quantity of desired
concentration can be weighed direct without
indirect determination (Standardization)

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Organic acids
Read and research more about organic acids,
theirs uses in pharmacy practice and their
neutralization power.

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