CHAPTER II

PHARMACEUTICAL AIDS AND

NECESSITIES
Official Inorganic Acids
Boric Acid
Hydrochloric Acid
Boric Acid NF 26
NF = National Formulary
Formulary =specify particular
medications that are approved to be
prescribed under a particular insurance
policy.

Boric Acid
Chem. Name: H3BO3
Mol. Weight: 61.83
Synonyms: Boracic Acid, Hydrogen
Borate, Orthoboric Acid
Occurrence: Free Boric Acid sea waters,
certain plants, nearly all fruits, some
volcanic steam jets
Boric Acid
Native Boric Acid (Sassolite)
Largest material source is in combined
forms e.g.
Na2 B4O7.4H2O (Rasorite or Kernite)
Na2 B4O7.10H2O (Borax)
CaB4O7.4H2O (Borocalcite)
Ca3B6O10.5H2O (Colemanite)
H3BO3.NaB4O7.2CaB4O7.18H2O (Tincal)


Boric Acid
Properties: solid available in 3 forms:
(1) colorless, odorless, pearly scales
(2) six-scaled triclinic crystals
(3) white, odorless powder w/c is unctuous
to touch (having a soapy feeling)
Boric Acid
The scale & crystalline forms of comp. are
more suitable for aqueous solns since
powder floats on top of water.
It is stable in air w/ a density: 1.46
Soluble(10 to 30 parts): water, alcohol,
Freely Soluble (1 to 10 parts): glycerin,
boiling water, and boiling alcohol

Boric Acid
Clear solns are obtained when 1g is
dissolved in 25mL of water
The addition of HCl decreases its solubility
in water.
Due to weak acid nature, only salts
produced by replacement of 1 proton per
molec. (primary salts) can be obtained
in aqueous soln

Boric Acid
Those salts formed w/ alkali metals are the
only ones soluble in water and these produce
very alkaline solutions
Salts formed w/ other metals are hydrolyzed
in water to produce insoluble hydroxides
Not absorbed through the intact skin but is
highly toxic ingested orally
Absorbed when applied over large areas of
broken skin

Boric Acid
Uses: NF XV specifies that Boric Acid
must contain n.l.t. 99.5% & n.m.t.
100.5% of boric acid calculated as an
anhydrous (dried) form
For years, it has been used as solns,
ointments, & dusting powder as an
antiseptic.
Boric Acid
At best, the comp. can be described as a
weak bacteriostatic (stops bacteria)
agents
It will still be found in the form of soln in
conc. From 2.5% to 4.5% for use as an
eyewash.
The more concentrated soln should be
diluted w/ an = vol. of water before use
Boric Acid
Higher conc. is near saturation and boric
acid tends to crystallize out w/ a slight
drop of temp.
This represents a danger & solns should
be warmed or diluted before use in order
to dissolve the crystals

Boric Acid
Used as a buffer in opthalmic solns &
prep. Like Aluminum Acetate Soln
USP XVIII & Aluminum Subacetate
Soln USP XVIII
USP - United States Pharmacopeia
Boric Acid
Since it is a weak acid, it constitutes a
portion of what would be required for a
buffer soln but used alone, it doesnt have
such buffer capacity
The rxn of boric acid w/ equimolar
quantities of glycerin at 140C- 150C
produces a comp. known as Boroglycerin
Glycerite NF XI (C3H5BO3)
Boric Acid
W/c has found some use as a suppository
base.
The toxicity of boric acid precludes its use
in products that are to be taken internally.

Boric Acid
Commercial Products:
Insecticides
Boric Acid
Commercial Products:
Fungicides
Boric Acid
Commercial Products:
Herbicides
Boric Acid
Commercial Products:
Antiseptic for minor burns or cuts
Boric Acid
Commercial Products:
Opthalmic Soln
Hydrochloric Acid NF 26
Synonyms: Muriatic Acid, Spirit of Sea
Salt, Marine Acid, Espiritu de Sal Marina
Official Definition: An aqueous soln
of hydrogen chloride gas containing n.l.t.
35% & n.m.t. 38% by weight of HCl
Properties: Colorless fuming liquid w/ a
pungent odor
Hydrochloric Acid NF 26
Specific Gravity: 1.18
A non-fuming soln can be prepared by
diluting it w/ 2 volumes of water
More highly ionized than most other
strong acids & attacks many metals w/
evolution of hydrogen
Hydrochloric Acid NF 26
Muriatic Acid (Latin: Muria brine) is a
technical grade of hydrochloric acid
containing 35% to 38% HCl & a no. of
impurities including chlorine, arsenous, &
sulfurous acids and iron
Impurities give yellow color
Hydrochloric Acid NF 26
Uses: Categorized by the NF XV as a
pharmaceutical aid or specifically as an
acidifying agent
By virtue of strong acid character, it reacts
w/ organic molecules w/c are weakly basic
to form usually water soluble
hydrochloride salts.
Hydrochloric Acid NF 26
This type of rxn is utilized to convert
normally water insoluble organic bases
into a water soluble form for extraction
or other separation purposes
Since salts of most organic amines are
solids, treatment of liquid organic bases
with hydrochloric acid can render the
comp. suitable for the incorp. into a
solid dosage form
Hydrochloric Acid NF 26
One disadvantage of using HCl for this
purpose is that some hydrochlorides are
hygroscopic (readily taking up and retaing
moisture). Nevertheless, most drugs are
available as hydrochloride salts are related
to their ease of preparation and to the very
low toxicity of the chloride ion.
Hydrochloric Acid NF 26
Diluted Hydrochloric Acid NF XV a
soln of hydrogen containing n.l.t. 9.5g &
n.m.t. 10.5g of HCl in each 100 mL of
soln
Diluted Hydrochloric Acid exists in the
normal gastric juice (about 0.2%) aiding in
the conversion of pepsinogen into
pepsin & proteids into peptones & as
gastric antiseptic
Hydrochloric Acid NF 26
It maybe valuable in some forms of
indigestion, especially in those conditions of
gastric achlorhydria (absence of
hydrochloric acid) & hypochlohydria
(deficiency of hydrochloric acid)
Usually given in doses from 1-10cc, highly
diluted w/ water and to be supplied through a
glass tube/ straw avoiding solvent action w/
on the enamel of the teeth.
Hydrochloric Acid NF 26
To avoid: prep. such as Glutamic Acid
Hydrochloride & Betaine Hydrochloride
have been advocated. They are crystalline
and maybe administered in capsule form.
They liberate HCl in the stomach, the
glutamic acid or betaine residue being
metabolized at the same time
Hydrochloric Acid NF 26
Commercial Products:
Muriatic Acid
Hydrochloric Acid NF 26
Other Uses:
Hydrochloric acid is a common laboratory
reagent.

NITRIC ACID NF 26
NITRIC ACID NF 26
HNO
3

Synonyms: Spirit of Nitre, Aqua Fortis, Agua Ferte

Properties:
aqueous solution; 68% < HNO3 < 71% by weight
highly corrosive fuming liquid, irritating odor
boiling point 120
o
C
specific gravity 1.41
on animal tissues
xanthoproteic test

NITRIC ACID NF 26
strong monoprotic acid
oxidizing and nitrating agent
photochemical decomposition of nitric acid
oxidized all common metals to produce nitrate
salt
Nitrating properties of nitric acid

NITRIC ACID NF 26
Uses:
Acidic properties similar to HCl
Acidifying agent in bases
Oxidizing and nitrating properties
Manufacture of sulphuric acid, coal tar dyes and
explosives
Nitrating agent in pyroxylin
External use: destroy chancres and warts

NITRIC ACID NF 26
Nylon, explosive, fertilizer, detergent
PHOSPHORIC ACID NF 26
PHOSPHORIC ACID NF 26
H
3
PO
4

Synonyms: Orthophosphoric Acid, Acido Orthofosforico

Properties:
Contains n.l.t. 85% and n.m.t. 88% by weight of H
3
PO
4
Colorless, odorless, syrupy liquid
Specific gravity: 1.71
Non-volatile and no oxidizing properties


PHOSPHORIC ACID NF 26

Uses:
Can be used as an acidifying agent
Can be treated with NaOH to produce mixtures pf HPO
4
-
2
and H
2
PO
4
-
Solvent in the preparation of Anileridine Injection NF
XV
DILUTED PHOSPHORIC ACID NF 26
Properties:
Contains n.l.t. 9.5 g and n.m.t. 10.5 g of H
3
PO
4
in 100 mL
of solution

Uses:
Used as a tonic and stimulant to the gastric mucous
membranes
Acts as synergistic to pepsin
Aids in the formulation of peptones
Used in making some pharmaceutical preparations

PHOSPHORIC ACID NF 26
Fertilizer,
cleaning
products, food
additive
SULFURIC ACID NF 26
SULFURIC ACID NF 26
H
2
SO
4

Synonyms: Oil of Vitriol, Vitriolic Acid, Aceite de Vitriolo

Properties:
Colorless, odorless liquid of oily consistency
Contains n.l.t. 94% and n.m.t. 98% of H
2
SO
4
Specific gravity: n.l.t. 1.84

oleum- commercial variety which contains about 10% of
dissolved SO
3

SULFURIC ACID NF 26

Preparation:
2 industrial processes of preparing sulfuric acid:
Contact or Catalytic Process and Lead Chamber
Process

Contact Process
- Produces most of the commercial sulfuric acid today

Lead Chamber Process
- Mainly used in the manufacture of the fertilizer



SULFURIC ACID NF 26

Uses:
Strong diprotic acid which can form salts of basic organic
drug molecules
Utilized as dehydrating agent in the preparation of
Pyroxylin USP 26
SULFURIC ACID NF 26
Fertilizer, lead-
acid battery,
drain cleaner
OFFICIAL
INORGANIC BASES
STRONG AMMONIA SOLUTION NF 26
STRONG AMMONIA SOLUTION NF 26
Synonyms: Ammonium Hydroxide, Stronger Ammonia Water

Properties:
Contains n.l.t. 27% and ammonia rapidly
Clear, colorless liquid, exceeding pungent, characteristic odor
Specific gravity: 0.90

Caution:
Be careful in handling because of the caustic nature of the
solution and the irritating properties of its vapors
STRONG AMMONIA SOLUTION NF 26

Can serve as a liquid in forming soluble complex ions
with many metal cations

Uses:
Used as Bronsted base to form ammonium salt of acids
Used in the manufacture of HNO
3
and NaHCO
3
Used in the preparation of Aromatic Ammonia Spirit NF
XV
STRONG AMMONIA SOLUTION NF 26
Fertilizer, cleaners
Diluted Ammonia
Solution
Also known as ammonia water or
household ammonia
it contains no less than 9 gram and not more
than 10 grams of NH3, with an appropriate
amount of purified water.
it is used in cleaning floors, walls, and some
appliances. Remove cloth and carpet stains.
Repels insects in drawers and closets.
Not to be used in contact with the skin and
eyes. Avoid breathing ammonia vapors, use
products in a well-ventilated area.

Calcium Hydroxide USP 31
Ca (OH)2; Mol. wt. 74.09
Also known as slaked lime or calcium
hydrate
- it is manufactured from lime or calcium
oxide through the addition of water in
limited amounts (slaking).

(Ca OH)2; Mol. wt. 74.09
- It is a solution containing not less than
140 mg of Calcium Hydroxide in each
100ml.
- Slaked lime or Calcium Hydrate is a
compound used to make mortars, plasters,
and cement. In dentistry, Calcium
Hydroxide is used as a root canal filling.
Potassium Hydroxide NF 26
KOH; Mol. wt. 56.11
Also known as Caustic Potash or
Potassa
-has characteristics of white fused masses,
small pellets, flakes, sticks that have a
crystalline fracture.
- it is a strong base that can cause
corrosive effects on the skin.






KOH; Mol. wt. 56.11
- it is used in bleaches and soaps, also used
as treatment for fungal infection on the
skin hair or nails.
- it is also used in veterinary as a form of
chemical cremation in order to hasten
the decomposition of the tissues of dead
animals, so that what is only left behind
are the bones and hard tissues.
Sodium Hydroxide NF 26
NaOH; Mol. wt. 40
Also known as Caustic Soda or Soda
Lye
Characterized as dry, hard, brittle, white
sticks fused in an opaque, white stone-like
masses in small pellets.
- it is a strong base, therefore it is capable
of damaging the skin.
Like Potassium Hydroxide, it is used
construction sites and the like.
Sodium Carbonate NF 26
Na2CO3H2O; Mol. wt. 124
Also known as monohydrated sodium
carbonate.
Classified as a colorless crystalline powder.
Exists in three characterized hydrates:
- Monohydrate-Na2CO3H2O
- Heptahydrate- -Na2CO37H2O
- Dedahydrate- -Na2CO310H2O
Sodium Carbonate is also commonly
known as washing soda or soda ash. It is
widely used as a cleaning agent at home,
but it has side effects that may cause
breathing problems, vomiting, diarrhea,
drooling and low blood pressure if
ingested.
Soda Lime NF 26
A mixture of calcium hydroxide and
sodium or potassium hydroxide or both.
Intended for use in metabolism tests,
anesthesia and oxygen therapy.
Soda Lime NF 26
Its function is to absorb carbon dioxide in
a closed system.
Will react with the carbon dioxide in the
form Na2CO3, to form calcium carbonate,
thereby regenerating the sodium
hydroxide.
Buffers
The Control of pH in solutions is very
important aspect of pharmaceutical
chemistry and practice.
Pair of related chemical compounds
capable of resisting large changes in the
pH of a solution caused by the addition of
small amounts of acid or base.
Buffers
Composed of weak acid or and its salt or
weak base and its salt.
Buffer should not react with:
1. Participate in oxidation-reduction
reaction
2. Alter the solubility of other components
3. Form complexes with active ingredients
Three Primary
Borate Buffer System
1. Feldmans buffer system (pH 7-8.2)
2. Atkins and pantin buffer system (pH 7.6-
11)
3. Gifford buffer system (pH 6-7.8)
Na
3
BO
3
NF 26 (Na
2
B
4
O
7
. 10H
2
O ; Mol. Wt.
381.37)
Synonyms: Borax, Sodium Pyroborate, Sodium
Tetraborate, Tinkal
Properties:
> colorless, transparent crystals or white crystalline
powder
> odorless and effloresces in warm, dry air
> soluble in water & glycerin ; insoluble in alcohol
> aqueous solutions are alkaline to phenolphthalein
> same toxicity as boric acid; hydrolyzed to boric acid
in aqueous solution

Na
3
BO
3
NF 26 (Na
2
B
4
O
7
. 10H
2
O ; Mol. Wt.
381.37)
Uses:
> best eyewash (acids mucosa)
> 1-2% solution collyria
> mouth washes, oral prep, powder (mouth ulcers)
> weak bacteriostatic agent
> borax soap - emulsifying agent preparation of
ointments (Cold Cream USP , Rose Water Ointment
NF)
>Washing soda

Antioxidants
Function: reducing agent
Used in pharmaceutical preparations
containing oxidizable substances to
maintain these substances in their
reduced form
Mechanism of antioxidant action may be
seen in two ways:
Either the antioxidant is oxidized
If active constituent is oxidized, the
antioxidant reduces it back to its normal
oxidation state
Antioxidants
Factors in selecting a suitable antioxidant:
Physiologically inert
Assessment of possible toxicity of reducing
agent & oxidized product
Possible solubility problems between
reducing agent and the drug
Formation of explosive mixture when the
very strong reducing agents are combined
with strong oxidizing agents
Antioxidants
Examples:
Vitamin E
Vitamin C
Fruits
Vegetables
Hypophosphorous Acid (HPH
2
O
2
or
H
3
PO
2
)
Properties:
Colorless or slightly yellow, odourless liquid
Contains not less than 30% and not more than 32% HPH2O2
Pure acid: syrupy colorless liquid; solid at 17 C, melts at 26C
oxidation state is 1+
powerful reducing agent
reduce compounds to form phosphorus acid (H3PO3) having
oxidation state of 3+ and phosphoric acid (H3PO4) having
oxidation state of 5+
net transfer of 4 electrons

Hypophosphorous Acid (HPH
2
O
2
or
H
3
PO
2
)
Uses:
no important pharmacological action
antioxidant
prevents the formulation of free iodine in Diluted Hydroiodic Acid
and Syrup
present in Diluted Ferrous Iodide Syrup NF XI prevents the
formulation of ferric ions and molecular iodine
Salts: antioxidant properties
Sodium Hypophosphate preservative in certain foods
Hypophosphorous Acid (HPH
2
O
2
or
H
3
PO
2
)
Uses:
Ammonium Hypophosphate
found in many preparations as
preservative
Hypophosphite never be
triturated with oxidizing agents
(nitrates, chlorates, or
permanganates)
Concentration ranges: never over
1%
Sulfur Dioxide (SO2)
Synonym: Sulfurous Anhydride
Properties:
Colorless, non-flammable gas
Strong suffocating odor characteristic of burning
sulfur
Soluble in water (36:1) forming sulfurous acid
(moderately strong acid)
Oxidation state is 4+
Strong reducing agent

Sulfur Dioxide (SO2)
Uses:
Antioxidant and pharmaceutical aid
Protects many susceptible compounds from oxidation
Reducing the oxidized firm back again
Reacting with oxygen before the susceptible compounds do
Used in injectable preparations because of its gaseous nature
Enclosed in single dose ampoules or in multiple does vials
Extensive use in industry: bleaching wood pulp, fumigating grains,
arresting fermentation
Fumigate houses burning of sulfur dioxide
SODIUM BISULFITE ( NaHSO3 )
Synonym: Sodium Hydrogen Sulfite, Sodium Acid
Sulfite, Leucogen
Properties:
Mixture of sodium bisulfite (NaHSO3) and sodium
metabisufite (Na2S2O5)
Compound is white or yellowish white crystals or a
granular powder
Odor of sulfur dioxide
Solid is unstable in air, giving off sulfur dioxide
Should yield not less than 58.5 % and not more
than 67.4 % sulfur dioxide
SODIUM METABISULFITE NF 26 ( Na2S2O5
)
Properties:
Compound is white crystal or white to yellowish
crystalline powder
Odor of sulfur dioxide
Should contain Na2S2O5 equivalent to n.l.t. 66%
and n.m.t. 67% sulfur dioxide
SODIUM METABISULFITE NF 26 ( Na2S2O5
)
Bisulfites
NaHSO3 is acidic enough to neutralize the stronger
bases (sodium bicarbonate) to form sulfite
Addition of sulfites to acidic solutions will result to a
shift in alkaline pH by the formation of bisulfite, w/c
reduces concentrations of hydrogen ions
One primary source of incompatibilities with
bisulfites and sulfites is solubility:
Salts of alkali metals soluble
Salts of alkaline earth metal bisulfites less
soluble
Sulfites of metals - insoluble
USES OF NaHSO3 and
Na2S2O5
Used almost exclusively as an antioxidant
Usually found in acidic solutions of drugs
that contain phenol or catechol nucleus to
prevent oxidation of compounds to quinines
May also be found in ascorbic acid as a
reducing agent
May be used to prepare water soluble
derivatives of normally insoluble drugs
NITROGEN (N
2
)
Molecular Weight = 28.01

Properties:
Colorless & odorless inert gas
Non-flammable and doesnt support
combustion
One volume dissolves in about 65 volumes
of H
2
O and in about 9 volumes of alcohol
at 20C and at the pressures of 760 mmHg
Sold in black cylinders
Uses:
Inert atmosphere to retard oxidation in
oxidation sensitive products(Cod Liver Oil,
Olive Oil, Multi Vitamins Preparations)
To replace containers for parenterals and
topical solutions
To retard oxidation for carbon monoxide
Water (H
2
O)
Molecular Weight = 18.01528

Properties:
Tasteless, odorless and clear liquid which
is colorless in small quantities but
greenish blue in deep layers.
Density is 1, ice= -1 ~ makes ice float in
water
Ability to form hydrogen bonds

Properties making water the solvent of
choice:
Constituent of the body
Having high dielectric constant
Being a small molecule
Why is dielectric constant important to
water?
It is important to its capacity as a solvent as a
stabilizer of structure. It is also responsible to
the non linear bent shape of water.
Hardness of water:
-this property of water is due to the presence
of varying amounts of Ca, Fe and Mg salts
which convert ordinary soap (water soluble Na
and/or K salts of high molecular weight fatty
acids) into water insoluble Ca, Fe and Mg salts
of fatty acids(water insoluble curd)

*Soap with hard water = Curdy Precipitate

Temporary hardness
-caused by the presence of
Ca(HCO
3
)
2
or Mg(HCO
3
)
2


-can be removed (softened) by
boiling or addition of a source of OH
-

Permanent hardness
-caused by the presence of SO
4
-2
, Cl
-

or OH
-
of Ca and or Mg

-can not be removed by boiling or
addition of a source of OH
-
Ways of purifying water:

Addition of soluble Carbonates which
precipitate Ca and Mg as insoluble
Carbonates
Ex. Washing Soda ( Na
2
CO
3
10H
2
O)
Ways of purifying water:

Chelation by zeolite (permutit) Process
Zeolite=Na
2
OAl
2
O
3
2SiO
2
3H
2
O
Passing the hard water through a zeolite column
an exchange of water hardening cations is made
for non-hardening sodium cations. When
calcium zeolite reaches a high enough
concentration the column can no longer exchange
calcium ion for sodium ion efficiently. To restore
its activity, a strong solution of NaCl is allowed to
flow through the inactivated zeolite reconverting
it to the Na form.


Ways of purifying water:
Deionizer/Demineralizer
Makes use of certain synthetic resins which
are endowed with removing both cations and
anions from water. Since the water produced
from this apparatus compasses very favorably
with distilled water at lower cost USP XX
modified the name and monograph of distilled
water to permit the use of deionized water
under the title of purified water.
Ways of purifying water:
Polyphosphate Chalation
The detergent industry has been using basic
phosphate and sodium meta-phosphate to
chalate the divalent calcium making it
unavailable for further reaction.
Ca & Mg made unreactive by chelate
bond(claw)
Official Waters
Purified Water USP 31

obtained by distillation and ion exchange
treatment
clear odorless liquid with specifications
for extemporaneous compounding
used in preparation of most USP test
reagents.
Water for Injection USP 31
purified by distillation
must pass two tests: Pyrogen test and
Endotoxin test
preparing extemporaneous parenterals
would more likely use
Bacteriostatic/Sterile water for injection

Sterile Water for Injection USP 31
sterilized water for injection
most difficult to prepare
used for compounding of parenterals
either IV or IM injection
no antimicrobial substance
Sterile Water for Inhalation USP 31
prepared from sterilized water for
injection
no antimicrobial agents
for inhalation therapy
packaging: glass or plastic container


Sterile Water for Irrigation USP 31
from sterilized water for injection
packaging: single-dose glass/ plastic
containers
no antimicrobial agents
Bacteriostatic Water
for Injection
sterile water for injection
with antimicrobial agents
used for parenterals for intramuscular
injection
not for use in newborns
Glass
generic term referring to vitreous
material
may be considered as sodium silicate
Most commercial ones are vitreous
silicates and some type of additive
Boron-decreases the coefficient of
expansion of Pyrex glass
Potassium-gives brown light-resistant
glass
Four Types of Glass
Type 1 highly resistant, borosilicate glass
Type 2 treated with soda lime glass
Type 3 soda lime glass
Type NP general soda lime glass
Types of Containers
Colorless
Opaque- superior light protective
Colored
Clear:
1. patient likes to see what he is buying
2. amount left in the bottle is seen
3. ease of pouring

Four Types of
Clear Containers
Colorless
Green
Blue
Amber screens
out UV radiation