PHARMACEUTICAL AIDS AND

NECESSITIES

Marie Faith G. Madamba, RPh

Definition: agents important to the preparation, preservation
and storage of pharmaceutical products
Classification:
1. Acids & Bases – frequently employed in the conversion of
drugs to chemical form convenient to their product
formulation.
2. Buffers –maintain the pH of various formulations within
prescribed limits.
3. Antioxidants – prevents oxidative decomposition of
pharmaceutically active components.
4. Waters – primary solvent or liquid phase in most liquid
pharmaceutical preparations.
5. Glass – for storage and as dispensing container for most
drug products.
OFFICIAL INORGANIC ACIDS
1. Boric Acid (H3BO3)
Synonyms: Boric Acid, Hydrogen borate, Orthoboric Acid
Occurrence: found in seawaters, certain plants, in nearly all fruits
and in some volcanic steam jets. Native boric acid is called
sassolite.
Properties: Available in three crystalline forms:
a. colorless, odorless, pearly scales
b. six-sided triclinic crystals
c. white, odorless powder which has a soapy feel
Uses: antiseptic because it is a weak bacteriostatic agent in 2.5%-
4.5% conc as eyewash, buffer in ophthalmic solutions.
Toxicity of boric acid makes it unfit to be taken orally.
2. Hydrochloric Acid (HCl)
Synonyms: Chlorhydric acid, Spirit of Sea Salt, Muriatic
acid
Uses: pharmaceutical aid as an acidifying agent

3. Diluted Hydrochloric Acid

Diluted HCl exists in the normal gastric juice aiding in
the conversion of pepsinogen into pepsin and proteins
into peptones and as gastric antiseptic.
Gastric achlorhydria – is absence of HCl
Hypochlorhydria – deficiency of HCl
4. Nitric Acid (HNO3)
Synonyms: Spirit of Nitre, Aqua fortis, Aqua fuerte
Properties: Nitric acid will produce a yellow stain on animal tissue due
to nitration of the aromatic amino acids, phenylamine, tyrosine, and
tryptophan found in the properties of skin. This is known as the
Xanthoproteic test.
Nitric acid is a strong monoprotic acid, an oxidizing, and nitrating
agent. It oxidizes common metals except gold and platinum to product
the nitrate salt of the metal.
Uses: it is use in the manufacture of sulfuric acid, coal tar dyes and
explosives. It is used as a nitrating agent in Pyroxylin USP XVII as a
source of nitrate ion in the preparation of Milk of Bismuth. It has been
used externally to destroy chancres and warts.
5. Phosphoric Acid (H3PO4)
Synonyms: Orthophosphoric acid, acido orthofosforico
Uses: acidifying agent

6. Diluted Phosphoric Acid

Uses: It is used as a tonic and stimulant to the gastric mucous membranes, acts as
synergistic to pepsin and aids in the formulation of peptones.

7. Sulfuric Acid (H2SO4)

Synonyms: Oil of Vitriol, Vitriolic Acid, Aceite de Vitriole
Preparation: 2 ways to prepare sulfuric acid:
Contact or Catalytic process and the Lead Chamber process. Both have the same
principle, that is, the oxidation of sulur dioxide to sulfur trioxide and adding enough
water to form sulfuric acid. In the catalytic process, vanadium and platinized silica gels
are used as catalysts.
Use: dehydrating agent in the preparation of Pyroxylin USP XX

8. Glacial Acetic Acid

OFFICIAL INORGANIC BASES
1. Strong Ammonia Solution (NH4OH)
Synonyms: Ammonium hydroxide, Stronger Ammonia Water
NF XV issues the following caution concerning strong ammonia solution: Use
care in handling because of the caustic nature of the solution and the
irritating properties of its vapor. Cool the container well before opening and
cover the closure with a cloth or similar materials while opening. Do not taste
or inhale the vapors.
Uses: Bronsted base; manufacture of nitric acid and sodium bicarbonate; in
preparing Aromatic Ammonia Spirit and Ammoniacal Silver Nitrate Solution.

2. Diluted Ammonia Solution

This is prepared from Strong Ammonia Solution and known as ammonia
water or household ammonia. It is employed as a circulatory stimulant by
inhalation of the vapors. Externally, it is used as counter- irritant.
3. Calcium Hydroxide (Ca(OH)2)
Synonyms: Slaked lime, Calcium hydrate
Preparation: Ca(OH)2 is manufactured from lime or calcium oxide
through the addition of water in limited amounts. The process is known
as slaking and is characterized by the avid absorption of water by the
oxide accompanied by the evolution of much heat, swelling of the
calcium oxide lumps and final disintegration into fine powder.

Uses: It is used medicinally as a fluid electrolyte and as a topical

astringent. It is used in pharmaceutical preparations for its potentially
high hydroxide ion conc. The alkalinity allows it to react with the free
fatty acids in various oils (e.g. oleic acid) to form calcium soaps, which
have emulsifying properties. It is combined with NaOH or KOH in a
mixture known as Soda Lime, which is used for its ability to absorb CO2
from expired air in metabolic function tests.
4. Potassium Hydroxide (KOH)
Synonyms: Caustic Potash, Potassa
Properties: It is very deliquescent and rapidly absorbs both moisture
and carbon dioxide from the air. It is a very strong base having a caustic
or corrosive effect on tissues. NF XV states, CAUTION: Exercise great
care in handling KOH as it rapidly destroys tissues.
Uses: It is used as a caustic principally in veterinary practice. It is used
in official preparations as a saponifying agent to hydrolyze esters of
fatty acids into their constituent alcohols and the potassium salt.

5. Sodium Hydroxide (NaOH)

Synonyms: Caustic soda, Soda lye
Properties: It attacks soft glass, so bottles, which are used as
containers, should be made of hard glass using rubber stopper. Glass
stoppered bottles can be used if a little petroleum or paraffin is spread
around the stopper.
Uses: same as with KOH but has more advantage over KOH since it is
less deliquescent, milder, and cheaper
6. Sodium carbonate (Na2CO3.H2O)
Synonyms: Monohydrated Sodium Carbonate
Uses: It is used for its basicity in pharmaceutical
preparations where it will form sodium salts of acidic
drugs.

7. Soda Lime
It is a mixture of Ca(OH)2 and NaOH or KOH both
intended for use in metabolism tests, anesthesia and
O2 therapy.
BUFFERS:
Buffers control the pH of a pharmaceutical product. The
reasons for controlling pH within certain specified limits are
for:
a. Chemical stability
b. Solubility of the drug
c. Patient’s comfort

Some factors, which can produce alterations in pH include:

a. Alkali in certain inexpensive containers
b. Gases present in air

Buffer systems are composed of a weak acid and its salt

(conjugate base) or a weak base and its salt (conjugate acid).
Mechanism of Action of Buffer Systems:
When small amounts of hydrogen ion are introduced into the medium
they will react with the conjugate base and basic members of the
buffer to form a weak acid, which, by definition will only slightly be
ionized. Similarly, when a small amount of hydroxide ion (base) is
introduced into the medium, they will react with the weak acid or
acidic member of the buffer pair and form water and the conjugate
base. Hence, each component of the buffer pair will react with either
acid or base to form the other component; thereby repressing large
changes in hydrogen ion concentration.

The selected buffer should not:

a. Participate in oxidation- reduction reaction
b. Alter the solubility of other components
c. Form complexes with active ingredients
Two Inorganic Buffer Systems:
a. Phosphate Buffer System
Advantages: contains the dihydrogen and monohydrogen
phosphate ions, one of the physiological buffer pairs normally
found in the body.
Disadvantages: insolubility of the phosphate salts of such metals
such as Ag, Zn, and Al and that it supports microbial growth.

b. Borate Buffer System

This is used in preparations containing metals that would
otherwise precipitate in the presence of phosphate. Since
borates are toxic, these buffer system are suitable in external
preparations, ophthalmic and nasal solutions but are
contraindicated in parenteral solutions.
Three Primary Borate Buffer Systems:
1. Feldman’s Buffer System (pH 7.6-8.2)
- Consists of acid solution containing boric acid, sodium
chloride (to make it isotonic) and the alkaline solution
containing sodium borate.

2. Atkins and Pantin Buffer System (pH 7.6-11)

- Consists of alkaline solution of sodium carbonate and acid
buffer solution of boric acid and sodium chloride.

3. Gifford Buffer System (pH 6 -7.6)

- Similar to Feldman Buffer System however in place of sodium
chloride, potassium chloride is used to make it hypotonic.
1. Sodium Borate (Na2B4O7.10H2O)
Synonyms: Borax, Sodium pyroborate, Sodium tetraborate, and
Tinkal
Uses: Sodium borate is one of the best eyewash when acids
happen to enter the mucosa. It is one of the components of
many mouthwashes and oral preparations and is frequently
applied in the form of powder to ulcers in the mouth. It is a weak
bacteriostatic agent. It forms borax soap, which serves as an
emulsifying agent in the preparation of ointments particularly
Cold Cream USP and Rose Water Ointment NF.
2. Hydrochloric Acid Buffer (pH 1.2 -2.2)
3. Acid Phthalate Buffer (pH 2.2 -4.0)
4. Neutralized phthalate buffer (pH 4.2- 5.8)
5. Phosphate Buffer (pH 5.8- 8.0)
6. Alkaline Borate Buffer
ANTIOXIDANTS:
Definition: are compounds which have the capability of functioning
chemically as reducing agents

Mechanism of Action of Antioxidants:

a. Either the antioxidant is oxidized in place of the active constituent
b. If the active constituent is oxidized, the antioxidant reduces it back
to its normal oxidation state.

In selecting a suitable antioxidant, the following factors should be

considered:
a. An antioxidant in a pharmaceutical preparation should be
physiologically inert.
b. the possible toxicity of both the reducing agent and its oxidized
product must be assessed.
c. One should consider possible solubility problems between the
reducing agent and the drug.
d. Very strong reducing agents will form explosive mixtures when
combined in dry form or in concentrated solution with strong
oxidizing agents.
1. Hypophosphorous Acid (HPH2O2)
Uses:
a. It serves to prevent the formation of free iodine in diluted
Hydroiodic Acid and syrup.
b. It is also present in Ferrous Iodide Syrup where it prevents the
formation of both ferric ions and molecular iodine.
c. Salts of hypohposphorous acid are also used for their
antioxidant properties.
d. Sodium hypophosphite is present as preservative in certain
foods.
e. Ammonium hypophosphite may also be found in many
preparations as preservative.
2. Sulfur dioxide (SO2)
Synonym: Sulfurous Anhydride
Uses:
a. It will protect many susceptible compounds from oxidation by
reducing the oxidized form back again or by reacting with oxygen
before the susceptible compounds do.
b. It is usually used in injectable preparations in ampules or vials.
c. It is used in industry to bleach wood pulp, fumigating grains and
arresting fermentation.

3. Sodium Bisulfite (NaHSO3) or Sodium Metabisulfite (Na2S2O5)

Synonyms: Sodium Hydrogen Sulfite, Sodium Acid Sulfate, and Leucogen
Uses:
a. It is used to prevent oxidation of the compounds of phenol or
catechol nucleus to quinones.
b. Bisulfites may also be found in ascorbic acid injections as a reducing
agent.
c. It is used to prepare water-soluble derivatives of normally insoluble
drugs.
d. Metabisulfite is found in ascorbic acid injection as a reducing agent.
4. Nitrogen (N2)
Uses: It is used as an inert atmosphere to retard oxidation in
oxidation-sensitive products. It is also used to replace air in containers
for parenterals and solutions for topical applications.

5. Sodium thiosulfate
Use: this is employed as an antidote for cyanide poisoning.

6. Sodium nitrite (Na2NO3)

Uses:
a. An antidote for cyanide poisoning
b. Nitrite are used in brine solutions for curing of meats and fish.
This is because it is an excellent color developer, enhances flavor
production and prevents against microbial growth. However,
nitrite ions remain in cured meats and react with organic amines
to form potentially carcinogenic N-nitrosamines.
GLASS:

Glass is employed as the container material of choice for most

small volume infusions. It is composed chiefly of silicon
dioxide, with varying amounts of other oxides like sodium,
potassium, calcium, magnesium, aluminum, boron, and iron.
Glass is formed by the silicon oxide tetrahedron. Boric oxide
will enter into this structure but most of the other oxides do
not
Glass Types:
1. Type I, Borosilicate glass
- This is composed principally of silicone dioxide and boric
oxide, with low levels of the non-network-forming oxides.
- It is chemically resistant glass (low leachability) also having
a low thermal coefficient of expansion.
- This type of container is suitable for all products although
sulfur dioxide treatment sometimes is used for a further
increase in resistance.

2. Type II, Soda-lime treated glass

3. Type III, Soda-lime glass
- These glasses are composed of relatively high proportions of
sodium oxide and calcium oxide. This makes the glass chemically
less resistant.
- They melt at a lower temperature, are easier to mold into various
shapes, and have a higher thermal coefficient of expansion than
Type I.
- Type II has a lower concentration of the migratory oxides than Type
III.
- Type II is treated under controlled temperature and humidity
conditions with sulfur dioxide or othe dealkalizers to neutralize the
interior surface of the container.
- Type II glass may be suitable for a solution that is buffered, has a
pH below 7, or is not reactive with the glass.
- Type III glass usually will be suitable principally for anhydrous
liquids or dry substances
4. NP, a soda- lime glass not suitable for containers for parenterals.
WATER:
 Water acts as a primary solvent for most substances due to
its properties: small size, strong permanent dipole, high
dielectric constant, and availability of protons for hydrogen
bonding.
 Pure water is a tasteless, odorless, clear liquid which is
colorless in small quantities and greenish blue in deep layers.
 Due to solvent powers and physiological inertness, water is
an extremely important pharmaceutical agent.
Natural Waters:
1. Alkaline Waters
- Usually contain appreciable quantities of sodium and
magnesium sulfates

2. Carbonated Waters
- Those which have been charged with carbon dioxide under
pressure while in the earth

3. Chalybdate Waters
- Contain iron in solution or in suspension and are characterized
by a ferrigenous taste (rusty).

4. Lithia Waters
- Occurs in the form of carbonate or chloride
5. Saline Waters
- Also known as “purgative waters”, contain relatively large
amounts of magnesium and sodium sulfates with sodium
chloride

6. Sulfur Waters
- Contain hydrogen sulfide

7. Siliceous Waters
- Cintain very small amounts of soluble alkali silicates
Official USP Waters:
1. Purified Water
2. Water for Injection
Description: clear, colorless, odorless liquid; purified by distillation or
reverse osmosis and contains no added substances.
Use: pharmaceutic aid as vehicle or solvent
3. Bacteriostatic Water for Injection
Description: sterile water for injection containing one or more suitable
antimicrobial agents
Use: sterile vehicle for parenteral preparations
4. Sterile Water for Injection
Description: clear, colorless, odorless liquid; water for parenterals;
sterilized; contains no antimicrobial agent or other added substance
Use: for preparation of all aqueous parenteral solution including those
used in animal assays.
5. Sterile Water for Irrigation
Description: clear, colorless, odorless liquid; water for injection
that has been sterilized; contains no antimicrobial agent or other
substance
Use: an irrigating solution
Label must say: For Irrigation Only and Not For Injection
6. Sterile Water for inhalation
Use: incorporated to nebulizer for asthmatic patient

Heavy Water – isotopes of hydrogen (deuterium and tritium)