MECHANISM OF ANTIOXIDANT ACTION
1. Antioxidant is oxidized in place of the active
constituent
2. If the active constituent is oxidized, the anti
oxidant reduces it back to its normal
oxidation state
Selecting a suitable antioxidant
1. An anti oxidant in a pharmaceutical
preparation should be physiologically inert
3. The possible toxicity of both the reducing
agent and its oxidized product must be
assessed
4. One should consider possible solubility
problems between the reducing agent and
the drug
5. Very strong reducing agents will form
explosive mixtures when combined in dry
form or in concentrated solution with strong
oxidizing agents
HYPOPHOSPHOROUS ACID NF XV
-HPH2O2
-MW 66
Properties:
-a colorless or slightly yellow, odorless liquid
containing not less than 30% and not more than
32% HPH2O2
-a specific gravity of 1.13 at 25C
-the pure acid is a syrupy colorless liquid, which
becomes a solid at 17C and melts at 26C
-the oxidation state of the central phosphorous
atom is for making the compound a very
powerful reducing agent
-it can reduce many compounds to form
phosphorous acid (H3PO3) having an oxidation
state of 3+ and finally phosphoric acid (H3PO4)
having an oxidation state of 5+ for a net transfer
of four electrons
-its reducing properties are readily illustrated by
its reaction with molecular iodine to form iodine
ions and its ability to decolorize acidic solutions
of potassium permanganate immediately.
Uses:
-Hypophosporous acid and its salts
(hypophosphites) have no important
pharmacological action
-principally as an antioxidant
--> prevent the formation of free iodine in
Diluted Hydroiodic Acid and Syrup
--> ferrous iodine syrup NF XI where it prevents
the formation of both ferric ions and molecular
iodine
-salts of hypophosphorous acid are also used for
their antioxidant properties
--> sodium hypophosphite - preservative in foods
--> ammonium hypophosphite - preservatives in
preparations
-Hypophosphites should never be triturated with
oxidizing agents such as NO3^-2, ClO3^- or
MnO4^-
-The concentration ranges for hypophosphorous
acid and its salts when used as antioxidants are
never over 1%
SULFUR DIOXIDE NF XV
-SO2
-MW 64.06
-Synonyms: Sulfurous Anhydride
Properties:
-colorless, non-flammable gas possessing a
strong suffocating odor characteristic of burning
sulfur
--> the same odor noticed from the burning of
high sulfur containing fuel
-contains not less than 97% by volume os SO2
-under pressure, sulfur dioxide condenses to a
colorless liquid which boils at -10C and has a
density of 1.5
-it is soluble in water (36:1) forming a
moderately strong acid-- sulfurous acid
-contains sulfur in the 4+ oxidation state and
functions as strong reducing agent
-when sulfur dioxide is passed through an
aqueous solution containing iodine, hydriodic
acid is formed
-with potassium permanganate, it is oxidized to
sulfate
Uses:
-classified as an anti oxidant pharmaceutical aid
--> protects many susceptible compounds from
oxidation by reducing the oxidized from back
again or probably even more important, by
reacting with oxygen before the susceptible
compounds do
Properties:
-(gaseous nature), sulfur dioxide is usually used
in injectable preparations enclosed in single dose
ampules or multiple dose vials
-finds extensive use in industry for such
processes as bleaching wood pulp, fumigating
grains and arresting fermentation
-it is also used to fumigate houses where it is
given off in the burning of sulfur candles
SODIUM BISULFITE NF XV
-NaHSO3
-MW 104.06
-Synonyms: Sodium Hydrogen Sulfate, Sodium
Acid Sulfite, Leucogen
Properties:
-The NF XV describes sodium bisulfite as a
mixture of sodium bisulfite (NaHSO3) and
sodium metabisulfite (Na2S2O5) in varying
proportion
-It is a white or yellowish white crystals or a
granular powder having the odor of sulfur
dioxide
-should yield not less than 58.5% and not more
than 67.4% SO2
-the solid is unstable in air, giving off SO2
SODIUM METABISULFITE NF XV
-Na2S2O5
-MW 190.10
Properties:
-white crystal or a white to yellowish crystalline
powder having the odor of sulfur dioxide
-it should contain an amount of Na2S2O5
equivalent to not less than 66% and not more
than 67% of SO2
-most commercial sodium bisulfite is actually the
metabisulfite. this salt can be used when
bisulfite is specified because when dissolved in
water, it is immediately converted to bisulfite
-Treatment of bisulfites or the normal salts
(sulfite) with aqueous acid yields sulfurous acid;
which is essentially a solution of SO2 in water
-Sodium bisulfite is acidic enough to neutralize
the stronger bases, e.g sodium carbonate to
form the sulfite
-on the other hand, the addition of sulfites to
acidic solutions will result in a shift towards
alkaline pH by the formation of bisulfite, which
reduces the concentration of hydrogen ions
-one primary source of incompatibilities with
bisulfites and sulfites is solubility. the only
soluble salts are those of the alkali metals.
-the alkaline earth metal bisulfites are less
soluble and the sulfites of the metals are
insoluble
-Antioxidant
--> found in acidic solutions of drugs that contain
the phenol or catechol nucleus to prevent
oxidation of the compouns to quinines (anti
malarial drug)
-also be found in ascorbic acid injections as a
reducing agent
-used to prepare water-soluble derivatives of
normally insoluble drugs
-example:
--> Menadione Sodium Bisulfite is converted to a
water-soluble form for preparing parenteral
products. The activity of menadione is
maintained until regenerated in the tissues.
NITROGEN NF XV
-N2
-MW 28.01
Properties:
-occurs as colorless, odorless, inert gas, non-
flammable and does not support combustion
-one volume dissolves in about 65 volumes of
water and in about 9 volumes of alcohol
-Nitrogen NF is usually sold in black cylinders
Uses:
-Nitrogen is used as an inert atmosphere to
retard oxidation in oxidation sensitive products
--> cod liver oil, olive oil, multiple vitamin
preparations, etc
-it is also used to replace air in containers for
parenteral and solutions for topical applications
-it is also used to retard oxidation in the
qualitative test for carbon monoxide
WATER
-primary solvent / liquid phase in most liquid
pharmaceutical preparation
Properties:
-tasteless, odorless, clear liquid which is
colorless in small quantity but greenish blue in
deep layers
-Water has the ability to form hydrogen bonds
with other water molecules or other
electronegative or positive ions or molecules
-Water has a high dielectric constant which is
extremely important to its capacity as a solvent
and stabilizer of structure
-The dielectric constant is related to the
separation of charge within the water molecule
as a result of its non-linear "bent" shape
-the combination of water being the predominant
constituent of the body, having a high dielectric
constant, being a small molecule and readily
forming hydrogen bonds makes water the
solvent of choice in most liquid dosage forms
-because its the predominant constituent of the
body, problems of toxicity, metabolism and
excretion of the solvent do not normally have to
be considered when water is used as a solvent
(70% water in the body)
-having a high dielectrical constant allows water
to solvate ions readily and to stabilize
macromolecules (proteins, etc)
-the small molecular size allows water to
penetrate into the free space within a crystal and
to break the ionic bond
Hardness of Water
-this property of water is due to the presence of
varying amounts of calcium, iron and/or
magnesium salts that convert ordinary soap
(water-soluble sodium and/or potassium salts of
high molecular weight fatty acids) into water
insoluble calcium, iron and/or magnesium salts
of fatty acids (water-insoluble curd)
1. Temporary Hardness (Bicarbonate
Hardness)
- is caused by the presence in the water of
calcium or magnesium bicarbonates and can
be removed (softened) by boiling or addition of
a source of hydroxide
2. Permanent Hardness
- caused by the presence in solution of sulfates,
chlorides or hydroxides of calcium and/or
magnesium, which cannot be removed by boiling
or addition of a source of hydroxide
Hardness of Water
-since many manufacturing laboratories
consume large amounts of water free from
dissolved solids and the process of distillation is
costly, other means of purifying water were
devised
1. ADDITION OF SOLUBLE CARBONATES
(E.G WASHING SODA)
-Which will precipitate calcium and magnesium
as insoluble carbonates
-Na2CO3 . 10H20 = Sal soda (washing soda)
2. CHELATION BY THE ZEOLITE (PERMUTIT)
PROCESS
-Zeolite is sodium silicate
-(Na2O.Al2O3.2SiO2.3H2O) with the symbol
Na2Zeol
3. DELONIZER OR DEMINERALIZER
-makes use of a certain synthetic resins, which
are endowed with removing both cations and
anions from water
4. POLYPHOSPHATE CHELATION
-the detergent industry has been using basic
phosphate and sodium metaphosphate to
chelate the divalent calcium making it
unavailable for further reaction
OFFICIAL WATERS
1. WATER USP XX
-clear, colorless, odorless liquid which has
specifications for pH, zinc, other heavy metals,
foreign volatile matter, total solid content and
bacteriological purity
-official as a solvent and is used to make official
solution, tinctures and extracts
2. PURIFIED WATER USP XX
-water of choice for extemporaneous
compounding and preparation of most USP test
reagents
--> obtained by distillation of by ion exchange
treatment
-it occurs as a clear, odorless liquid which has
specifications for pH, chloride, sulfate, total
solids, ammonia, calcium, carbon dioxide, heavy
metals, oxidizable substances and
bacteriological purity
3. WATER FOR INJECTION USP XX
-water purified by distillation
-meets all the specifications called for in the
purified water monograph and must pass a
pyrogen test (rabbit)
-intended for use as a solvent for the preparation
of parenteral solutions
-label must indicate that no antimicrobial
substance has been added
-used for extemporaneous compounding of
parenterals for either intravenous or
intramuscular injection
-finished preparations should be sterilized
-used by large-scale pharmaceutical
manufacturers
-a pharmacy preparing extemporaneous that escapes into the air when the plumbing line
parenterals would be more likely use is opened, giving a distinct "rotten egg" smell
bacteriostatic water for injection or sterile water
for injection 8. Siliceous water
-contains soluble alkali of silicates
4. STERILE WATER FOR INJECTION USP
-water for injection sterilized and suitably
packaged
-most difficult to prepare
-maybe stored in single-dose containers of not
larger than 1000ml size

5. BACTERIOSTATIC WATER FOR INJECTION

USP XX
-sterile water for injection containing one or
more suitable antimicrobial agents
-Benzyl Alcohol is a common bacteriostatic agent
--> not used for IV administration
-stored in single-dose or in multiple-dose
containers of not larger than 30 ml size
-intended for compounding small volumes of
extemporaneous parenterals for intramuscular
injection
(for children - gastric syndrome)

TYPES OF WATER

1. Mineral Water
-Natural spring or well water which contain in
solution sufficient quantity of mineral or gaseous
matter that would render them until for domestic
use.

2. Alkaline water
-contains sodium + magnesium sulfates together
with bicarbonates.

3. Carbonated water
-Charged with CO2 under pressure
-Effervescence upon contact with surface

4. Chalybeate Water
-ions in water or in suspension charged by a
ferroginous taste

5. Lithia Water
-occurs in the form of carbonates or chlorides

6. Saline Water
-"purgatives waters"
-Magnesium + sodium sulfate with sodium
chloride

7. Sulphur Water
-It is a condition where the running water
contains a high amount of hydrogen sulfide gas