Pharmaceutical Manufacturing (Laboratory)

Supplemental Notes

M.O # 1 – SODIUM PHOSPHATE SOLUTION

Formulation for 60 mL:

Sodium Phosphate - Active Ingredient

Citric Acid, USP - Preservative
Glycerin - Humectant
Sodium benzoate - Anti fungal Preservative
Purified Water - Solvent

Description: Clear, colorless liquid with a thick syrupy consistency, odorless, cooling saline
taste, specific gravity of 1.39 @ 25°C, acidic to litmus, and effervesces with sodium carbonate

Mode of Preparation: Simple Solution

Use: An orally administered saline laxative used primarily in preparation for surgery,
endoscopy or x-ray. It is usually effective overnight or within one hour if taken before meals.

Laxative: pertaining to a substance that causes evacuation of the bowel by mild action,
increase bulk of feces by softening the stool and by lubricating the intestinal wall.

Cathartic: a substance that aids bowel movement by exciting intestinal waves.

Categories:

a. Stimulant laxatives
● Work by inhibition of absorption, enhancement of secretion and effects on motility
● Examples: bisacodyl, phenolphthalein and senna
b. Saline laxatives
● Exert an osmotic effect that increase the water content and volume of stool
● Examples: magnesium citrate and sodium phosphate
c. Hypertonic laxatives
● Exert and osmotic effect leading to water secretion into the intestines
● Example: lactulose
d. Bulk-forming laxatives
● Undigestible substances that tend to absorb water, increase the bulk of stool and
inhibit the bile absorption
● Examples: cellulose derivatives and psyllium
e. Lubricant laxatives
● Agents that allow easy passage of stool by oil coating and they also inhibit colonic
reabsorption of water
● Example: mineral oil

Dose: Adult dose is 20-30 mL mixed with ½ glass of water and follow with glassful of water.
Over 10 years old – 10mL
5-10 years old – 2.5 to 5mL

Contraindication: it should not be used in patients with abdominal pain nausea or vomiting.

Sodium Phosphate (Na2HPO4 • 7H2O)

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Synonyms: disodium salt heptahydrate, dibasic sodium phosphate, disodium

orthophosphate, disodium hydrogen phosphate, secondary sodium phosphate.
Preparation: it was prepared from bone phosphate or bone ash and from
mineral phosphorite or tribasic calcium phosphate.
Description: Colorless or white granular salt; effloresces in warm dry air;
solutions are alkaline to litmus and phenolphthalein
Solubility: 1g in 4 mL water, very slightly soluble in alcohol
Caution: This phosphate should not be confused with tribasic sodium
phosphate which is very alkaline and has caustic action.

Citric Acid- used as a preservative and is added to prevent the salt from crystallizing.

Glycerin- used as a humectant and it also prevents bacterial formation.

Sodium Benzoate- used to prevent mold formation.

SOLUTIONS
- A homogenous mixture that is prepared by dissolving a solid, liquid, or gas in
another liquid and represents a group of preparations in which the molecules of the solute
are dispersed among those of the solvent.

- Liquid preparations that contain one or more chemical substances dissolved in a

suitable solvent or mixture of mutually miscible solvents.

Solubility: indicates the maximum concentration to which a solution may be prepared with
a solute and a solvent.

Parts of solvent required

Description
For 1 part solute
Very soluble <1
Freely soluble 1-10
Soluble 10-30
Sparingly Soluble 30-100
Slightly Soluble 100-1,000
Very Slightly Soluble 1,000-1,0000
Practically Insoluble 10,000 up

Factors Affecting solubility:

1. Temperature
2. Physico-chemical properties of solute and solvent
3. Pressure
4. pH
5. Particle size of solute
6. Physical Agitation
ADVANTAGES OF SOLUTION

◻ Because solutions are molecularly dispersed system, they offer this advantages:
🞑 completely homogenous doses

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🞑 immediate availability for absorption and distribution

◻ Solutions also provide a flexible dosage form
🞑 they may be used by any route of administration
🞑 they can be taken or administered by patients who cannot swallow tablets or
capsules.
🞑 doses are easily adjusted

DISADVANTAGES OF SOLUTION

◻ drugs are less stable when in solution than when in dry form;
◻ some drugs are not soluble in solvents that are acceptable for pharmaceutical use;
◻ drugs with objectionable taste require additives or techniques to mask the taste
when in solutions;
◻ because solutions are more bulky and heavy than dry solid dosage forms, they are
more difficult to handle, pack, store and transport;
◻ oral solutions in bulk containers require measurement by the patient this is often less
accurate than individual solid dosage forms such as tablet and capsules.

METHOD OF PREPARATIONS

1. Simple solution- prepared by dissolving solute in suitable solvent.

Ex: Calcium Hydroxide Solution
2. Solution by chemical reaction- prepared by reacting 2 or more solutes in each
other in a suitable solvent.
Ex. Sodium citrate solution; Aluminum Subacetate Solution
3. Solution by Distillation- distilling the volatile principles from a drug inside a copper
wire cage which allows the free passage of vapors and boiling water.
4. Solution by Extraction- it is a process for crude drugs either of vegetable or animal
origin extracted in water. Resulting solution is extractive. Ex: Liver Solution, NF

M.O # 2 – AMMONIUM CHLORIDE EXPECTORANT SYRUP

Formulation for 60mL:

Ammonium Chloride, USP - Active Ingredient (Expectorating agent)

Sodium Citrate, USP - Alkalizing agent
Citric Acid, USP - Acidulant
Sodium Benzoate - Antifungal preservative
Glycerin - Humectant
Ethyl Alcohol, 95% - Solvent/preservative
Lemon Oil - Flavorant
Simple Syrup - Flavored vehicle/preservative
Purified water - Solvent

Mode of Preparation: Simple Solution

Use: Expectorant

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Dose: 10-15mL three to four times a day

Storage: Cool temperature (8-15°C)

EXPECTORANTS- are drugs that have been useful in loosening and liquefying mucus, in
soothing irritated bronchial mucosa and in making coughs more productive.

Action of Expectorants:
1. Decrease the viscosity of bronchial secretions and facilitate their elimination so that
local irritants are removed and ineffectual coughing is alleviated or made more
productive.
2. By increasing the amounts of respiratory tract fluid so that demulcent action is exerted
on the dry mucosal lining, thus relieving the unproductive cough

Humidification of room and adequate fluid intake (6-8 glasses) can effectively liquefy
respiratory mucus and have useful therapeutic effects.

Ammonium Chloride (NH4Cl)

Synonyms: Muriate of ammonia, Sal ammoniac

Description: Colorless crystals or a white fine or coarse crystalline powder,
cool saline taste, somewhat hygroscopic, when dissolved in water the
temperature of the solution is lowered, pH 4.6-6
Solubility: 1g in 3mL water, 100 mL alcohol, 8mL glycerin
Use: Expectorant, Diuretic Systemic acidifier

SYRUP

◻ are concentrated aqueous preparations of a sugar or sugar substitute with or without

added flavoring and medicinal agents
🞑 it is an 85% w/solution of sucrose in purified water.
◻ COMPONENTS OF SYRUP
🞑 Medicinal agent
🞑 sugar substitute (dextran)
🞑 non-sugars (sorbitol, glycerin and propyleneglycol)
🞑 antimicrobial preservatives
🞑 Flavorants
🞑 Colorants
🞑 some other special solvent solubilizing agent; thickness; stabilizers

3 KINDS
◻ Simple syrup- (Syrup NF)- basis for the preparation of flavored or medicated water
alone. It is quite resistant to microbial growth (85 sucrose in 100mL of water
requires no preservatives. With a specific gravity of 1.313.
◻ Medicated syrup- aqueous solution of sucrose containing added medical substance
and in addition to sucrose containing added medical substance and other polyols
such as glycerin or sorbitol maybe added to retard crystallization of sucrose or to
increase the solubility of added ingredients.

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◻ Non medicated/Flavored syrup- contains aromatic and pleasantly flavored

substances and is intended as a vehicle or flavored Rx.
◻ Cherry syrup – vehicle for drugs that are stable in acidic medium
◻ Orange syrup – vehicle for drugs that are stable in acidic medium
◻ Cocoa syrup – used to mask the bitter taste of drugs
◻ Raspberry syrup – used to mask the sour or salty taste of saline medicaments
◻ Acacia syrup – used to mask the bitter taste of Vitamin-B complex preparations
◻ Aromatic eriodyctyon syrup – used to mask the bitter taste of alkaloids

PREPARATION OF SYRUP
◻ solution with the aid of heat
🞑 method of choice if desired to prepare the syrup as quickly as possible and
when drug components is not volatilized by heat;
🞑 caution should be monitored to avoid invertion of sugar
🞑 ex. Cocoa syrup NF; Syrup USP 85% sugar
◻ solution by agitation without the aid of heat ex. Ferrous sulfate used as hematinic;
citric acid syrup
◻ addition of sucrose to a medicated liquid or to flavored liquid: fluidextracts, tinctures
or other liquids are added
◻ Percolation: it permits purified water or aqueous solution to pass slowly through a
bed of crystalline sucrose to dissolve it ex. Tolu balsam syrup

Problems encountered
✔ Due to excessive heating: sugar (sucrose) is hydrolyzed and it produces dextrose
(glucose) + fructose (levulose) and they are classified as invert sugar.
✔ The sweetness is altered
✔ Invert sugar is sweeter than the sucrose
✔ Colorless syrup darkens due to levulose
✔ Overheating may become amber color due to caramelization of sucrose

Types of preservative used for low concentration of syrup

◻ Benzoic acid 0.1 to 0.2%
◻ Na Benzoate 0.1 to 0.2%
◻ Methyl, propyl, butyl parabens 0.1%

M.O # 3 – TRISULFAPYRIMIDINES ORAL SUSPENSION

Formula for 100mL:

Sulfadiazine, USP - Active Ingredient (Antibacterial)
Sulfamerazine, USP - Active Ingredient (Antibacterial)
Sulfamethazine, USP - Active Ingredient (Antibacterial)
VeeGum - Suspending agent
Simple syrup, 85% - Flavored vehicle
Sodium citrate - Buffering agent
Sodium benzoate - Preservative
Vanilla Flavor - Flavorant

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ORAL SUSPENSIONS
- are liquid preparations that consist of solid particles dispersed throughout a liquid
phase in which the particles are not soluble. Suspending agents are added to ensure
appropriate dispersion of the solid in the vehicle.

Some suspensions are prepared and ready for use while others are prepared as solid mixtures
intended for reconstitution just before use with an appropriate vehicle.

A properly prepared suspension has a number of desirable properties:

1. The suspended material do not settle rapidly
2. Particles that settle rapidly must not form a hard cake and should be easily
resuspended uniformly upon shaking.
3. The suspension should pour freely from the container

Insoluble powders that do not disperse evenly throughout the suspending medium, when
shaken, should be powdered finely and levigated with a small amount of an agent such as
glycerin, alcohol or a portion of the dispersion of the suspending agent.

Other ingredients are incorporated and the remainder of the dispersion of the suspending
agent incorporated gradually by trituration to produce the appropriate volume.

SULFADIAZINE (C10H10N4O2S)
Synonym: benzenesulfonamide, 4-amino-N-pyrimidyl
Structural formula:

Description: white or slightly yellow powder, odorless or nearly odorless.

Stable in air but slowly darkens on exposure to light; melts between 251-
254°C.

Solubility: 1g in 13,000 mL water, 620 mL human serum at 37°C. Sparingly

soluble in alcohol and acetone. Freely soluble in dilute mineral acids, solutions
of Potassium and Sodium hydroxides or Ammonia TS.

SULFAMERAZINE (C11H12N4O2S)
Synonym: Benzenesulfonamide, 4-amino-N-(4-methyl-2-pyrimidinyl-)-sulfamethyldiazine.
Structural formula:

Description: white or faintly yellowish crystals or powder slightly bitter taste,

odorless or nearly odorless, stable in air but slowly darkens on exposure to
light, melts between 234-239°C.

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Solubility: 1 gram in 6250mL water, readily soluble in dilute mineral acids or

solutions of potassium, sodium, ammonium hydroxides, slightly soluble in
alcohol, very slightly soluble in ether and chloroform.

SULFAMETHAZINE (C12H14N4O2S)
Synonym: Benzenesulfonamide, 4-amino-N-(4,6-dimethyl-2-pyrimidinyl)-sulphadimidine.
Structural formula:

Description: white or yellowish white powder which may darken on exposure

to light, slightly bitter taste, melts between 197-200°C.

Solubility: Very slightly soluble in water or ether; slighlty soluble in alcohol,

soluble in acetone

M.O. # 4 – MENTHOLATED CHEST RUB OINTMENT

Formulation:
Menthol - active
Eucalyptus oil - active
Turpentine oil - active
Oil of wintergreen -
Paraffin - stiffening agent
Petroleum jelly - ointment base

Method of Preparation: Fusion

Use: It is intended for the relief of pulmonary congestions in colds and allergy. It stimulates
nerve endings for colds, and is used as a local analgesic and counterirritant.

Menthol
Synonym: Peppermint camphor
Chemical formula: C10H20O
Uses:
● In low concentration, it selectively stimulates the sensory nerve endings for cold and
hence causes a sensation of coolness.
● It also has local analgesic effect making it useful for the treatment of insect bites and
stings, itching, minor burns and sunburn, hemorrhoids, toothache, cold sores and sore
throat.
● In high concentration, it stimulates sensory nerve endings for heat and pain and may
cause irritation.
● Rubbing of menthol-containing ointment in the chest possesses to relieve pulmonary
congestion in colds and allergy and also for muscle aches.

Eucalyptus oil
Preparation: A volatile oil distilled with steam from the fresh leaves of Eucalyptus globules
and contains not less than 70% of eucalyptol.
Component: The most important constituent is eucalyptol.

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Incompatibility: It may be toxic.

Uses:
● Flavoring agent.
● Expectorant in chronic bronchitis.
● Bacteriostatic agent.

Turpentine oil

Ointments
Synonym: Unguents
Definition: Are semisolid preparations intended for external application to the skin or mucous
membranes. They should soften but not necessarily melt when applied to the skin.

Types of Ointments
● Medicated ointments
● Nonmedicated ointments

Classification of Ointment Bases

● Hydrocarbon or Oleaginous Bases
o Characteristics: Hydrophobic, emollient, occlusive and greasy
o Examples: Yellow ointment, white ointment, white wax, petrolatum, white
petrolatum, mineral oil, spermaceti
● Absorption Bases
o Characteristics: Anhydrous, absorbs small amount of water, emollient,
occlusive and greasy
o Examples: Anhydrous lanolin (woolfat), hydrophilic petrolatum
● W/O Emulsion Bases
o Characteristics: Emollient, occlusive, greasy
o Examples: Cold cream, lanolin (hydrous wool fat)

● O/W Emulsion Bases

o Characteristics: Non-emollient, non-greasy, non-occlusive, can be diluted with
water
o Examples: Vanishing cream and hydrophilic ointment
● Water-Soluble or Greaseless Bases
o Characteristics: Non-greasy, non-occlusive, water-washable, only water-
washable components can be added
o Examples: PEG ointment

Methods of Preparation
● Incorporation
● Fusion

Packaging
● Collapsible tubes
● Ointment jars

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