Pharmaceutical aids-and-necessities

Pharmaceutical
aids and
necessities

OBJECTIVES
 At the end of the unit, the students should be able
to:
 Identify the different pharmaceutical aids and
necessities
 Describe the properties of different
pharmaceutical aids
 Discuss the importance and application of
pharmaceutical aids and necessities to
pharmaceutical preparations/

Overview
 Pharmaceutical aids and necessities are
agents important to
 Preparation
 Preservation
 Storage of pharmaceuticals.

Classification
 Acids and bases
 Buffers
 Antioxidants
 Water
 Glass
 NO therapeutic value
 For making dosage forms

ACIDS, BASES, AND
BUFFERS
 Bronsted-Lowry theory is the acid base theory we
use in the pharmacy because physiologic
functions and pharmaceuticals are often times
dispensed as an aqueous solution.
 General chemical expression:
HA + B = Aˉ + HB˖
 Acid + Base = conjugate base + conjugate acid

Electrolytes
 Strong acids and bases are strong electrolytes
 Weak acids and bases are weak electrolytes
 Relation
 The stronger the acid, the weaker its conjugate
base, and vice versa.
 The stronger the base, the weaker its conjugate
acid, and vice versa.

Boric acid (H3BO3)
 Synonym: boracic acid, hydrogen borate, orthoboric acid
 Occurrences: found in seawaters, certain plants, in nearly
all fruits and in some volcanic stem jets. The nativ 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 with a soapy feel
Uses: antiseptic because it is a weak bacteriostatic agent; in
2% w/c concentration as eyewash and as buffer in opthalmic
solutions
*the toxicity of boric acid makes it unfit to he taken orally.

Hydrochloric acid (HCl)
 Synonym: chlorhydric acid, spirit of sea salt,
muriatic acid
 Use: a pharmaceutical aid as an acidifying
agent

Diluted Hydrochloric acid
 Diluted HCl exists in the normal gastric juice
aiding in the conversion of pepsinogen into
pepsin and of proteins into peptones and
serving as a gastric antiseptic. It is also used
in the management id gastric achlorhydria,
the absence if HCl in the stomach; and
hypochlorhydria, the deficiency of HCl
production of the stomach.

Nitric acid (HNO3)
 Synonym: spirit of nitre, aquafortis, aqua fuerte
 Properties: nitric acid will produce a yellow stain on
animal tissue due to the nitration of the aromatic amino
acid, phenylamine, tyrosine and tryptophan found in the
proteins of skin. This reaction is known as xanthoproteic
test. It oxidizes common metals except gold and
platinum to produce the nitrate salt of the metal.
 Uses: the manufacture of sulfuric acid, coal tar dyes and
explosives; a nitrating agent in pyroxylin USP XVIII; a
source of nitrate ion in the preparation of milk of
bismuth; externally, the elimination of chancres and
warts.

Phosphoric acid(H3PO4)
 Synonym: orthophosphoric acid, acido
orthofosforico
 Use: acidifying agent

Diluted phosphoric acid
 Uses: a tonic and stimulant to the gastric
mucous membranes; a synergistic substance
to pepsin and acids to the formulation of
peptones

Sulfuric acid (H2SO4)
 Synonym: oil of vitriol, vitriolic acid, aceite de vitriole
 Preparation: there are two ways to prepare sulfuric
acid: contact pr catalytic process and the Lead
chamber process. Blth have the same principle, that
is, the oxidation of the sulfur dioxide to sulfur trioxide
by adding enough water to form sulfuric acid. In the
catalytic process, vanadium and platinized silica gels
are catalyst.
 Use: dehydrating agent in the preparation of
pyroxylin USP XX

Acetic acid (CH3COOH)
 Synonym: glacial acetic acid
 Use: irrigation solution with some
bacteriostatic properties

1. Strong Ammonia Solution
2. Diluted Ammonia Solution
3. Calcium Hydroxide
4. Potassium Hydroxide
5. Sodium Hydroxide
6. Sodium Carbonate
7. Soda Lime
8. Potassium Bicarbonate
9. Sodium Bicarbonate

Strong Ammonia Solution (NH4OH)
USP38/NF33
Other Names:
 Ammonium Hydroxide
 Stronger Ammonia Water
Precautions:
 Use care in handling (caustic nature and
irritating properties of its vapor)
 Cool the container well before opening
 Cover the closure with cloth while opening
 Do not taste or inhale the vapors

Bronsted base
Manufacture of nitric acid and sodium
bicarbonate
Preparation of aromatic spirit
Preparation of ammoniacal silver nitrate
solution

Tollens' reagent is an alkaline solution of ammonia cal
silver nitrate and is used to test for aldehydes

Diluted Ammonia Solution
(NH4OH)
USP38/NF33
 Prepared from strong ammonia solution
 Known as ammonia water or household
ammonia
 Employed as circulatory stimulant through
inhalation of vapors
USES
 When used externally, it is counter-irritant

Calcium Hydroxide Ca(OH)2
USP38/NF33
Other Names:
 Slaked lime
 Calcium hydrate
Preparation:
 Manufactured from lime or Calcium Oxide by
slaking process.

Medicinally used as fluid electrolyte and topical
astringent
Utilized for its high hydroxide ion concentration in
pharmaceutical preparations.
Its alkalinity reacts with free fatty acids in various
oils to form calcium soaps which have emulsifying
properties.
Due to its ability to absorb CO2
from expired air, it is combined
with NaOH or KOH in a
mixture known as soda lime

Potassium Hydroxide (KOH)
USP38/NF33
Other Names:
 Caustic potash
 Potassa
Properties:
 Deliquescent
 Very strong base with caustic/ corrosive effect
on tissues (handle carefully)

Uses:
 As a caustic in veterinary practice
 As a saponifying agent to hydrolyze esters of fatty
acids into their constituent alcohols and potassium
salt

Sodium Hydroxide (NaOH)
USP38/NF33
Other Names:
 Caustic soda
 Soda lye
Properties:
 It attacks soft glass (containers should be made of
hard glass with rubber stoppers
 Glass-stoppered bottles can be used if a liitle
petroleum or paraffin is spread around the stopper
 Not borosilicate, a soft glass has high coefficients
of thermal expansion; thus it does not require a
high temperature to make them soft.

Uses:
 same as potassium hydroxide but has more
advantage since it is less deliquescent,
milder, and cheaper.

Sodium Carbonate
(Na2CO3.H2O)
USP38/NF33
Other Names:
Monohydrated sodium carbonate
Use:
In pharmaceutical preparations,
its basicity forms sodium salts of
acidic drugs

Soda Lime USP38/NF33
Uses:
 A mixture of Ca(OH)2 and NaOH or KOH or
both intended for metabolism tests,
anesthesia, and O2 therapy.

Potassium Bicarbonate
USP38/NF33
Other Names:
Potassium Hydrogen Carbonate
Potassium Acid Carbonate
Use:
Buffering agent for
pharmaceutical preparations

Sodium Bicarbonate
USP38/NF33
Other Name:
Sodium Hydrogen Carbonate
Use:
Preferred in preparation of effervescent
mixtures containing sodium bicarbonate
and organic acids such as tartaric or
citric. These additives react to liberate
CO2 that acts as a disintegrator
producing effervescence when in water.

A buffer is a solution of a weak acid and its salt or the salt
of its conjugate base or a weak base and its salt or the
salt of its conjugate acid that resists drastic changes in pH
when small amounts of acid or base are added to it.
Buffers control the pH of pharmaceutical products within
certain specified limits for these reasons:
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 such as CO2 and NH3

MECHANISM OF ACTION
 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.
 Similarly,when small amounts of hydroxide ion are
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

If base (OH) is added, it will react with the acid to
neutralize the base, forming acetate ion and water
H2C3O2 + OH → C2H3O2 + H2O
The selected buffer should not:
A. Participate in oxidation-reduction reaction
B. Alter the solubility of other components
C. Form complexes with active ingredients

EXAMPLES:
ACETIC ACID AND ITS CONJUGATE BASE,
ACETATE ION:
HC2H3O2 (acid) + H20 → H3O + C2H3O2
(conjugate base)
If acid (H3O) is added, it will react with the
conjugate base to neutralize the acid, forming
acetic acid and water
C2H3O2 + H3O → HC2H3O2 + H2O

Consider the following when choosing a buffer:
1. Volatile species should not be used as buffers
2. It should not have any influence on the
pharmacological activity of the API
3. The use of the pharmaceutical should be considered
in choosing a buffer for a product. If it is to be
ingested, buffers containing borates should not be
used as they are toxic systemically.

TWO INORGANIC BUFFER SYSTEMS
A. PHOSPHATE BUFFER SYSTEM
ADVANTAGE: it contains dihydrogen and
monohydrogen phosphate ions which are found
normally in the body
DISADVANTAGE: The insolubility of the
phosphate salts of such metals such as Ag, Zn,
and Al support microbial growth
B. BORATE BUFFER SYSTEM
It contains metals that would precipitate in
the presence of phosphate.
They are toxic and it is suitable in external
preparations, ophthalmic, and nasal solutions but
is contraindicated in parenteral solutions.

THREE PRIMARY BORATE BUFFER
SYSTEMS:
1. FELDMAN’S BUFFER SYSTEM
- pH of 7.6 – 8.2
- consists of : BORIC ACID, NaCl ( to make it
isotonic), and Sodium Borate
2. ATKINS AND PANTIN BUFFER SYSTEM
- pH of 7.6 – 11
- consists of: Sodium carbonate, Boric acid, and NaCl
3. GIFFORD BUFFER SYSTEM:
- pH of 6 – 7.6
- similar to Feldman’s Buffer System but NaCl is
replaced by KCl to make it hypotonic

STANDARD BUFFER SOLUTIONS
Buffer systems in pharmacy can be roughly categorized into:
1. Standard buffer systems – designed to provide a solution
having a specific pH for analytical purposes.
2. Actual pharmaceutical buffers – designed to maintain pH
limits in drug preparations
Standard buffer solutions having pH ranges between 1.2 and
10.00 can be prepared by appropriate combinations of:
- BORIC ACID AND POTASSIUM CHLORIDE, 0.2M
- HYDROCHLORIC ACID, 0.2M
- POTASSIUM CHLORIDE, 0.2M

- POTASSIUM PHOSPHATE, MONOBASIC 0.2M
- POTASSIUM BIPHTHALATE, 0.2M
- SODIUM HYDROXIDE, 0.2M
- ACETIC ACID, 2N
All the crystalline reagents except boric acid should be dried
at 110 – 120 degrees Celsius for an hour before use.
The water should also be CO2-free.
The solution should be stored in Type 1 glass bottles and the
solutions used within 3 months.
The solutions, prepared and standardized, will later be
combined in specific quantities to make the following
standard buffer solutions to achieve a certain pH.

F
BUFFER pH COMPOSITION
HYDROCHLORIC ACID 1.2 -2 50ml KCl solution with a
specified volume of 0.2 HCl
and water
ACID PHTHALATE BUFFER 2.2-4.O 50 ml of potassium
biphthalate solution with a
specified volume of 0.2 HCl
and water
NEUTRALIZED PHTHALATE BUFFER 4.5-5.8 50 ml of potassium
biphthalate with a specified
volume of NaOH and water
PHOSPHATE BUFFER 5.8-8.0 50 ml of monobasic
potassium phosphate with
NaOH and water
ALKALINE BORATE BUFFER 8.0-10.0 50ml of boric acid and KCl
with NaOH and water
ACETATE BUFFER 4.1-5.5 Specified amount of sodium
acetate with acetic acid and
water

• REDUCING AGENTS
• Pharmaceutical necessity

MECHANISM OF ACTION OF
ANTIOXIDANTS
• Either the antioxidant oxidizes in place of the
active constituent or inversely, the antioxidant
reduces the already oxidized active constituent
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 agent will form
explosive mixtures when combined in dry form or
in concentrated solution with strong oxidizing
agents

USES:
• The formation of free iodine is prevented in diluted
hydriodic acid and syrup.
• Its presence in ferrous iodide syrup ensures the
non-formation of both ferric ions and molecular
iodine.
• Salts of hypophosphorus acid are antioxidants.
• Sodium hypophosphite is a preservative in certain
foods.
• Ammonium hypophosphite is likewise a
preservative in many preparations.

Sulfur dioxide (So2
SYNONYM : Sulfurous anhydride

USES:
• It will protect many susceptible compounds from
oxidation by reducing oxidized forms back to their
original compounds or by reacting with oxygen
before the susceptible compounds do.
• It is usually in injectable preparations in ampules
or vials.
• It is used in industry to bleach wood pulp, to
fumigate grains and to arrest fermentation

Sodium bisulfite (NaHSO3) or
SODIUM
METABISULFITE(Na2S2O5)
SYNONYMS: SODIUM HYDROGEN SULFITE,
SODIUM ACID SULFITE AND LEUCOGEN

USES:
• It prevents oxidation of the compounds of
phenol or catechol nucleus to quinones.
• Bisulfite may also be found in ascorbic acid
injections as a reducing agent.
• It prepares water-soluble derivatives of
normally insoluble drugs.
• Metabisulfite is an ascorbic acid injections as
reducing agent.

Uses:
• As an inert atmosphere, it retards oxidation in
oxidation-sensitive products, and replaces air
in containers for parenterals and solutions for
topical applications.

Uses:
• Contains sulfur in two different oxidation
states.
• The oxidized sulphur atom is in a +6 state
resisting further oxidation, whereas the
remaining sulphur atom is in a zero oxidation
state. This oxidation polarity allows the
compound to act as a reducing agent. Also,
sodium thiosulfate acts as an antidote for
cyanide poisoning.

Uses:
• Nitrites can act as both a reducing and oxidizing
agent. Reduction of compounds with sodium
nitrite results in formation of nitrates.
• It is an antidote for cyanide poisoning.
• Nitrites in brine solutions are curing ingredients of
meats and fish for they are excellent color
developer, enhance flavor production, and
prevent microbial growth. However, nitrite ions
remain in cured meats and react with organic
amines to form potentially carcinogenic N-
nitrosamines.

 Red or Pink
Substance added Color imparted
Copper(I) oxide Opaque red, green, blue
Tin (IV) oxide Opaque
Calcium Fluoride Milky white
Manganese (IV) oxide Violet
Cobalt (II) oxide Blue
Finely divided gold Red, Purple, Blue
Uranium compounds Yellow, Green
Iron (II) compounds Green
Iron (III) compounds) Yellow
Chromium Green
Cadmium sulfide Yellow
Selenium Red or Pink

• Glass is 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.
• The following are added to imaprt color to the
glass

• Glass is formed by the silicon oxide
tetrahedron. Though boric oxide will enter
into this structure, most of the other oxides
do not.
• Glass types are determined from the result of
two USP tests: the powdered glass test and
water attack test. The latter is used for type II
glass.

• Selecting the appropriate glass composition is critical
facet of determining the overall specifications for each
parenteral formulation.
• Source or cause of leachables/extractables,
adsorption formulation components, especially
proteins, and cracks or scratches.
• Leachability- is a property in which ions from the
glass container will leach out and interact with the
product, thereby reducing the stability of the product.
 Delamination or glass particulate formation- is
caused by the chemical attack on the glass matrix by
the formulation solution, resulting in the weakening of
the glass and eventual dislodgement of flakes from the
glas surface.

TYPE I – Borosilicate glass
• Composed principally of silicon dioxide and
boric oxide, with low levels of the non-
network-forming oxides, it is a chemically
resistant glass (low leachability) with low
thermal coefficient of expansion.
• This type of container is suitable for all
products although sulfur dioxide treatment
sometimes is added to further increase its
resistance.

TYPE II – Soda-lime treated
glass
• The relatively high proportions of sodium
oxide and calcium oxide makes this glass
type chemically less resistant.
• Type II melts at lower temperature, rendering
it easier to mold into various shapes; and has
a higher thermal coefficient of expansion
than Type I.
• It has a lower concentration of the migratory
oxides than Type III.

• This type is treated under controlled
temperature and humidity conditions with
sulfur dioxide or other dealkalizers to
neutralize the interior surface of the
container.
• Type II glasses may be suitable for a
solution that is buffered, has a pH below 7, or
is not reactive with glass.

TYPE III – Soda-lime glass
• These glasses are composed of relatively high
proportions of sodium oxide and calcium oxide,
a combination that renders the glass chemically
less resistant.
• They melt at lower temperature, are easier to
mold into various shapes, and have a higher
thermal coefficient of expansion than Type I.
• Type III glasses are suitable principally for
anhydrous liquids or dry substances.
• 4. NP – Soda- lime glass not suitable for
containers for parenterals

Reagents added to modify the
characteristics/appearance of glass
Special
addition/Composition
Desired Property
Large amounts of PbO with
SiO2 and Na2CO3
Brilliance, Clarity, Suitability
for optical structures;
crystals or flint glass
SiO2, B2O3, and small
amounts of Al2O3
Small coefficient if thermal
expansion; borosillicate
glass
One part SiO2 and four
parts PbO
Ability to stop (absorb) large
amounts of X-rays and
gamma rays: lead glass
Large concentrations of
As2O3
Transparency to infrared
radiation

 Water acts as a primary solvent for most
substances due to its properties: small size,
string permanent dipole,high dielectric
constant and availability for 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 water
 Alkaline water- usually contain appreciable quantities of
sodoum and magnesium sulfates
 Carbonated waters- charged with carbon dioxide under
pressure while in earth.
 Chalybdate waters- have iron in solution or in suspension
and are characterized by a ferrigenous taste.
 Lithia waters- occur in the form of carbonate or chloride
 Saline waters- also known as "purgative waters" , hold
relatively large amount of magnesium and sodium sulfates
with sodium chloride.
 Sulfur waters- have hydrogen sulfide
 siliceous waters- include very small amounts of soluble
alkali silicates.

Official USP waters
 Most liquid injections are quite dilute; the
component present in the highest proportion
 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 a vehicle or solvent

• 3.) Bacteriostatic water for injection
Description : it is prepared from water for injection
that is sterilized and packaged in prefilled syringes
or in vials containing not more than 30 mL. It also
has one or more suitable antimicrobial agents.
Use: sterile vehicle for parenteral preparations
NOTE: label should state: "NOT FOR USE IN
NEONATES" as there were problems encountered
with neonates and the toxicity of the bacteriostat,
benzyl alcohol.

• 4.) Sterile water for injection
• Description: clear colorless odorless liquid for
parenterals; sterilized; no antimicrobial agent or other
added substances
• 5.)Sterile water for irrigation
Description: clear, Colorless, odorless liquid; water for
injection that has been sterilized; no antimicrobial agent
or other substances
Use: an irrigating solution
NOTE: label must say "For irrigation only and not for
injection"

 6.) Sterile water for inhalation
Description: it is prepared from water for injection, sterilized
and packaged,with no added antimicrobial agents.
Heavy water is isotopes of hydrogen (deuterium and tritium)

Pharmaceutical aids-and-necessities

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