Liquid Orals: Solutions, Syrups, Elixirs

Krupanidhi College of Pharmacy, Bangalore, India
Unit 4: Liquid Orals
Definition: These are the products which are used orally. They include,
solutions, gargles, mouth washes, glycerins, throat paints, aromatic waters,
syrups, elixirs, and emulsions.
4.1 What are pharmaceutical additives / excipients / adjuvants /
necessities, give their ideal requirements. 5 M.
1. Additives are the substances that are used to prepare a dosage form using a
drug. Example: Crocin syrup is prepared using paracetamol, sugar, water,
color, flavor and preservative.
2. Additives should have the following ideal qualities.
3. They should be inert and should not have any medicinal action.
4. They should have good smell, taste and color.
5. They should be cheap.
6. They should be readily available.
7. They should be compatible with other ingredients of the product.
8. They should not affect the bio availability of the product.
4.2. Write short notes on vehicles / preservatives / anti - oxidants /
sweetening agents / flavoring agents / coloring agents (each 5M).
Vehicles / Solvents:
1. These are the substances that carry the drug to the patient. Example: In
peppermint water, purified water is the vehicle.
2. The vehicles used in liquid products are purified water, aromatic waters,
non medicated elixirs, non medicated syrups, co solvents like alcohol,
glycerol, propylene glycol etc.
3. Purified water is made from drinking water by distillation or ion exchange
process or reverse osmosis technique. It has a pH of 4.5 to 7.
4. Aromatic waters are saturated solutions of volatile substances. Example:
Chloroform water, peppermint water.
5. Non medicated elixirs are sweet hydro alcoholic liquids. They are used as
vehicles for drugs having poor water solubility. Example: Paracetamol elixir.
6. Non medicated syrups are sweet viscous liquids. They are used as vehicles
to mask the unpleasant taste of the drug. Ex: cherry syrup, orange syrup,
lemon syrup, etc.
7. Non aqueous solvents like alcohol, glycerol, propylene glycol, poly ethylene

glycol are used along with water to dissolve the drugs.
8. Water for injection and oily liquids are used as vehicle for injections.
Preservatives:
1. These are the substances that prevent bacterial growth in dosage forms.
2. Example: Benzoic acid, sodium benzoate, methyl paraben, propyl paraben,
phenyl mercuric acetate, phenyl mercuric nitrate.
3. They should interfere with the growth and multiplication of microorganisms.
4. They should kill a wide variety of microorganisms at low concentration.
5. They should be non toxic.
6. They are added to dosage forms containing water as vehicle, because micro
organisms readily grow in water.
7. When a product contains more than 10 % alcohol, preservatives are not
required, because alcohol can kill microorganisms.
Antioxidants:
1. They are added to prevent degradation of drugs by oxidation.
2. Reducing agents like ascorbic acid, sodium bi sulphite protect the drug from
oxidation. They get oxidized and protect the drug.
3. True antioxidants like tocopherols block the oxidative chain reaction and
protect the drug.
4. They should be effective in low concentration.
5. They should be effective at a wide pH range.
6. Complexing agents like EDTA, trap metal impurities in product and prevent
oxidative degradation of drugs.
Organoleptic additives: Sweetening, flavoring and coloring agents are called
as organoleptic additives.
Sweetening agents:
1. These are substances added to liquid orals and chewable tablets.
2. Sweet taste is acceptable by all people. Hence it is used in dosage forms.
3. It is used to mask the bad taste of the drug.
4. Examples: sugar, liquid glucose, saccharin, aspartame.
5. Simple syrup is a saturated solution of sucrose. The problem with syrups is
cap locking and microbial growth.
6. Saccharin is a synthetic sweetener. It is 250 to 500 times sweeter than
sugar, but has a bitter after taste. 1 g of saccharin is equal in sweetening
power of 500 g sucrose.
7. Saccharin is used in products for diabetic patients.

Krupanidhi College of Pharmacy, Bangalore, Karnataka, India
Flavoring agents:
1. These are added in a liquid products and chewable tablets to mask the
bitter taste of the drug.
2. Example: Orange flavor, lemon flavor, chocolate flavor, vanilla, pine apple,
honey, mint, banana, ginger, etc.
3. To mask salt taste of a drug, use cinnamon flavor, orange flavor.
4. To mask bitter taste of a drug, use chocolate flavor.
5. To mask acid or sour taste, use fruity flavor.
6. Oily taste can be masked by mint flavor
7. For external products, perfumes like jasmine, rose, lavender etc. are used.
Coloring agents:
1. These are used in liquid products and tablets, semi solid products.
2. They are not used in injections.
3. They are used to give an attractive color to the product.
4. They should produce a very good color with small quantities.
5. Examples of natural coloring agents are: red ferric oxide, yellow ferric oxide,
chlorophyll, carotene, cochineal, tyrian purple.
6. Examples of synthetic coloring agents are: fast green, sunset yellow,
amaranth, etc.
7. There should be matching between color and flavor of the product.
8. Example: Products containing chocolate flavor should be colored red or
brown.
9. Example: Products containing orange / lemon flavor should be colored
yellow to orange.
10. Example: Products containing mint/vanilla flavor should be colored
white.
4.3 Discuss about solutions with an example, 5M.
1 They are liquid preparations for oral use. They contain a drug, sweetening
agent, flavoring agent, preservative, coloring agent and vehicle. Generally,
purified water is the vehicle.
2 Examples: Aromatic waters, syrups and elixirs.
3 Solutions are homogenous and easy to swallow.
4 Solutions are bulky to carry and drug degradation is fast.
5 Note: Discuss about the above products depending on marks.

4.4: Discuss about syrups. 10 M.
1. Syrup is a saturated solution of sugar in water. It has a concentration of 85
% w/v or 66.7 % w/w. The formulae are given below. (Solubility of sucrose
in water is: 2 g sugar will dissolve in 1 ml water or 200 g sugar will dissolve in
100 ml water).
Simple syrup, USP
S.NO Ingredient Quantity Purpose
1 Sugar 85 g Sweetening agent
2 Purified water q.s 100 ml Vehicle
Preparation: Sugar is dissolved in sufficient water to produce 100 ml by
agitation method.
Simple syrup I.P
S.NO Ingredient Quantity Purpose
1 Sugar 66.7 g Sweetening agent
2 Purified water q.s 100 g Vehicle
Preparation method: Sugar is dissolved in sufficient water to produce
100 g by agitation method.
3. It is impossible to dissolve a drug in syrup. So, the drug is dissolved in
a small quantity of water, and the flavoring syrup is added.
4. Dilute sucrose solutions are excellent media for microorganisms, but
saturated sugar solution is self preservative. It has high osmotic
pressure and microorganisms are killed. Hence, syrups are self preservative.
5. Advantages of syrups:
a. Pleasant product for bitter tasting drugs.
b. Easy to swallow by children and elders.
c. They do not contain alcohol.
d. They are self preservative.
6. Disadvantages:
a. Not suitable for diabetic patients.
b. If syrup is not saturated with sugar, microbial growth will take place.
c. Crystallization of sugar may take place in syrup. Add glycerin or sorbitol
to solve this problem.
d. Due to pleasant taste, children tend to take more leading to over dosage.
7. Formulation of syrups: They have drug, preservative, flavor, color,

stabilizers and vehicle.
8. Preparation methods:
a. Solution with the help of heat: In this method 66.7 g of sugar is
dissolved in 33.3 g of water with the help of heat, weight of syrup is
adjusted to 100 g with sufficient water.
b. Solution with agitation: In this method 66.7 g sugar is dissolved in 33.3
g of water by agitation for long time. Then, it is filtered using a cotton
plug and transferred to bottles.
c. Percolation method: In this method, water is percolated through a
column of sucrose. As water flows down, it dissolves the sugar and syrup
comes out from the bottom of column.
4.5 Discuss about elixirs 10 M.
1. They are clear, sweet, hydro alcoholic solutions for oral use. Ex: paracetamol
elixir
2. Advantages of elixirs:
a) Elixirs are less sweet and less viscous than syrup. They contain a co solvent
around 10 to 12 % alcohol, glycerol or propylene glycol.
b) When a drug has poor solubility in water, we cannot prepare a solution. In
such cases, alcohol /glycerol/propylene glycol is used along with water to
dissolve the drug.
c) Hydro alcoholic environment maintains both water soluble and alcohol
soluble drugs in solution.
d) They are easy to prepare when compared with syrups.
e) Preservatives are not needed in elixirs because the alcohol will act as a
preservative.
3. Disadvantages of elixirs:
a. They are less sweet than syrups since they contain less amount of sugar.
b. They are less effective in masking the taste of drugs.
c. As elixirs contain alcohol, excess sugar cannot be used as sweetening agent.
Sugar has less solubility in alcohol. Saccharin has to be used as a
sweetener.
d. Elixirs are costlier than syrups.
4. Elixirs are classified into non medicated and medicated elixirs.
5. Non medicated elixirs do not have any drug and are used as vehicles. Ex:
Aromatic elixir, Compound benzaldehyde elixir, Iso alcoholic elixir.
6. Medicated elixirs: Ex: Chloropheniramine maleate elixir, piperazine citrate

elixir, Terpin hydrate elixir.
7. Formulation: They have drug, co solvent, sweetener, flavor, color,
stabilizers and vehicle.
8. Method of preparation: Elixirs are prepared by simple dissolution with
agitation. Ingredients are dissolved in their respective solvents and the
solutions are mixed. Alcohol soluble ingredients are dissolved in alcohol,
water soluble ingredients are dissolved in water and the two solutions are
mixed.
4.6: Solubility of solids in liquids / factors affecting solubility of solids in
liquids / methods to increase solubility of solids in liquids.
1. Solubility: The concentration of solute in a saturated solution is called
solubility. Example: solubility of paracetamol is 1.5 g in 100 ml water at 20 OC.
Many pharmaceutical products are solutions of solid drug in water.
2. The various factors influencing solubility of solids in liquids are
3. Particle size: Solubility increases with reduction in particle size.
4. Solvent: Polar substances have more solubility in polar solvents. Non polar
solutes have more solubility in non-polar solvents. Like dissolves like.
5. pH of solvent: If the solute gets ionized at the pH of solvent, solubility will be
more. Example: Salicylic acid has more solubility in basic liquids and less
solubility in acidic liquids.
6. Example: Tetracycline is a basic drug, and has more solubility in acidic
liquids and less solubility in basic liquids.
7. Temperature: Generally solubility of solid increases with temperature.
8. Electrolytes: Presence of electrolytes reduce solubility of drugs in water due to
salting effect.
9. Co solvents: Alcohol, glycerol, increase solubility of drugs in water, and this is
called co-solvency.
10. Surfactants: Surfactants increase solubility of drugs by micellar
solubilization technique.
11. Polymorphism: Many drugs exist in different crystalline forms. This
phenomenon is called polymorphism. Example: Riboflavin crystal form II is
more water soluble than other forms.
12. Amorphous forms are more water soluble than the crystalline form in water.
Example: Amorphous novobiocin is more soluble than crystalline form in water.
13. Salt forms: If a drug has poor solubility in water, it can be converted into a
salt. Example: Sodium salicylate is more soluble than salicylic acid in water.

4.7: Evaluation of solutions / liquid orals: The various important quality
control tests carried out on liquid orals are given below.
1. The product is evaluated for drug content. The product is suitably diluted and
drug content is measured by UV analysis or HPLC analysis. The drug content
should be within the official limits.
2. The color, odor and taste of the product is evaluated physically.
3. The color can be measured by using a colorimeter.
4. The pH of the product is measured using a pH meter. It should be within the
specified limits.
5. The density of the product is measured using a specific gravity bottle. It should
be within the specified limits.
6. The viscosity of the product is measured using a viscometer. It should be
within the specified limits.
7. In case of syrups, the sugar concentration is measured using a suitable
analytical method. If the sugar concentration is less than 66.67 % w/w,
microbial growth will occur.
8. In case of elixirs, the alcohol concentration is measured using a suitable
analytical method.
9. Microbial load is measured by agar plate method. The product is inoculated in
a nutrient media and is incubated. Then it is observed for microbial growth
and it should be within the prescribed limits of 100 cfu/ml. (Colony forming
units = cfu). Further it should be free of Escherichia coli microorganism.
10. In case of suspensions, settling velocity and ease of re dispersibility is
measured.
11. Sedimentation parameters are used to evaluate stability of suspensions.
12. They are sedimentation volume (F) and degree of flocculation (β).
13. Sedimentation volume = F = Vu / V0.
14. V0 = Initial volume of sediment, Vu = Ultimate or final volume of sediment.
15. Degree of flocculation = β = Fflocculated suspension / Fdeflocculated suspension.
16. In case of emulsions, rate of creaming and globule size is evaluated by
microscopy method.
17. Stability of emulsions can be evaluated by microscopy, extent of phase
separation, centrifugation and freeze thawing method.
18. Microscopy: In this method, the size of 100 globules is measured by using
an eye piece micrometer. The average size and standard deviation is
calculated. The smaller the average size, the better the emulsion. This is

because, creaming will be less with smaller globules. If standard deviation is
less, it indicates that the globules are uniform in size.
4.8: Filling of liquid orals:
• Filling of liquid orals into bottles is done by gravimetric filling, volumetric filling
and constant level filling.
• This type of filling is used for viscous liquids. In this method, a particular
weight of liquid is filled into the container.
• In volumetric filling method, a given volume of liquid is filled into the container
using a piston. Each filling station is fitted with a piston and cylinder. The
liquid is sucked from the tank into a cylinder and by the stroke of the piston
the liquid is filled into the bottle. The fill amount depends on the stroke of the
piston and can be varied depending on the capacity of the bottle.
1 In this method, each container is filled to the same level, hence it is also
called fill to a level method. It uses the container for controlling the filling of
each container.

Emulsions
Introduction: An emulsion has two immiscible liquids, one dispersed in
another. It is stabilized by addition of an emulsifying agent. Example: Milk,
liquid paraffin emulsion, castor oil emulsion.
Properties of a good emulsion:
1. Creaming in emulsions should be slow, so that a dose can be taken.
2. Cracking should not take place in emulsions.
3. It should be easily pour able to take a dose.
4. It should have an elegant appearance.
5. It should have acceptable color, odor and taste.
Types of emulsions:
a. Oil in water emulsions, O/W emulsion: This emulsion has oil as an internal
phase (dispersed phase) and water as external phase (dispersion medium).
Example: Milk, Liquid paraffin emulsion.
b. Water in oil emulsions: This emulsion has water as internal phase
(dispersed phase) and oil as external phase (dispersion medium). Example:
Turpentine liniment.
c. O/W cream: It is a semi solid emulsion of oil in water. Example: Vanishing
cream like Fair and lovely, ponds vanishing cream.
d. W/O cream: it is a semi solid emulsion of water in oil. Example: Ponds cold
cream. It is used in winter season on the skin. On application, it leaves a
thin layer of oil on the skin and prevents water loss from the skin. This
prevents skin dryness.

Determination of type of emulsion:
1. Miscibility test: Emulsions can be diluted with the external phase. If an
emulsion can be diluted with water, it indicates that the emulsion is an o/w
emulsion. If we try to dilute o/w emulsion with oil, the oil will get separated.
Similarly, a w/o emulsion can be diluted with oil but not water.
2. Staining test: Dissolve scarlet red in oil and prepare an emulsion, then
observe it under a microscope. If the globules are red colored, it indicates
that the emulsion is o/w, otherwise it is w/o emulsion.
3. Electrical conductivity test: Water is a conductor of electricity,
whereas oil cannot conduct electricity. An electrical arrangement
containing a lamp, power supply and two electrodes is used in this test.
Electrodes are dipped in the emulsion, if the light glows, it indicates that
the emulsion is o/w type, otherwise it is o/w emulsion.
Formulation additives used in emulsions: The different ingredients required
for an emulsion are given in below table.
S.NO Ingredient Purpose Example
1 Drug It gives the required
medicinal action
Liquid paraffin oil,
Castor oil, olive oil,
arachis oil
2 Emulsifying
agent
To get a stable emulsion Acacia, spans,
tweens, bees wax,
wool fat, wool
alcohols.
3 Thickening
agents
To increase viscosity of
emulsion and reduce
creaming.
Tragacanth, xanthan
gum, sodium CMC
4 Coloring agents To give a color to
emulsion.
Rarely used, because
emulsions have a good
white color.
5 Sweetening
agents
To give a sweet taste to
emulsion.
Saccharin sodium
6 Flavor To give a pleasant flavor to
emulsion.
Vanilla flavor
7 Preservative To prevent microbial
growth
Sodium benzoate
8 Solvent Vehicle Purified water

Emulsifying agents:
1. It is the most important ingredient in an emulsion. When an oil and water
are shaken together, they disperse in each other. If we stop shaking, they
separate immediately into two layers.
2. An emulsifying agent or emulgent is added to prevent the separation of oil
and water.
3. An emulgent forms a thin layer around the globules and prevent them from
merging with each other.
4. The classification of emulgents with examples is given below.
S.NO Class Sub class and example
1 Natural products Acacia, tragacanth, sodium alginate, pectin,
agar, bees wax, wool fat, wool alcohol.
2 Semi synthetic poly
saccharides:
Methyl cellulose, sodium carboxy methyl
cellulose.
3 Surface active
agents (anionic
surfactants)
Sodium sterate, calcium sterate, sodium
lauryl sulfate.
4 Surface active
agents
Example : cetrimide is cationic surface active
agent
5 Non ionic
surfactants
Spans, Tweens, Macrogol esters, Macrogol
ethers
6 Finely divided
solids:
Bentonite, aluminum hydroxide, magnesium
hydroxide.
7 Others Saponins and carbomer
8 O/W emulgents Acacia, methyl cellulose, macrogol esters,
macrogol ethers, tweens, saponins.
9 W/O emulgents Calcium sterate, glycerol esters, spans, higher
fatty alcohols.

Preparation of emulsions: Emulsions are prepared by wet gum method, dry
gum method, bottle method. In wet gum method and dry gum method, first a
primary emulsion is prepared. This primary emulsion is diluted to get the final
emulsion.
The set ratio to prepare a primary emulsion is given below.
Oil: Water: Gum for fixed oils is 4:2:1
Oil: Water: Gum for mineral oils is 3:2:1
Oil: Water: Gum for volatile oils is 2:2:1
Wet gum method:
1. Take the acacia gum in a mortar. Add water as per set ratio, and triturate to
get mucilage.
2. Now add the oil in small quantities with constant trituration.
3. If the emulsion tends to become ropy, add a few drops of water and continue
trituration till emulsion is reformed.
4. When all the oil has been added, triturate vigorously for a few minutes.
5. Now dilute the primary emulsion with small quantities of water.
6. Transfer to measuring cylinder, rinse mortar and make up to volume.
Dry gum method:
1. Take the oil in the mortar. Add acacia gum as per set ratio to the mortar
and mix gently until there are no acacia lumps.
2. Now add all water at once, triturate continuously in a single direction until
a white, viscous, primary emulsion is formed.
3. When the primary emulsion is formed, there is a cracking sound, continue
trituration for another two minutes.
4. Dilute the primary emulsion by gradual addition of water with trituration.
5. Transfer the emulsion to measuring cylinder, rinse the mortar and make up
to volume.
Bottle method:
1. In a mortar, take the oil and soap and mix until there are no lumps.
2. Take water in a bottle, now add the above oily suspension in small
quantities and shake vigorously after each addition.
3. After all the oily suspension has been added, adjust to volume.

4. If oily suspension is taken in bottle and water is added in small quantities,
phase inversion will take place.
Stability problems in emulsions / Instabilities of emulsions / physical
stability of emulsions:
1. The various stability problems of emulsions are creaming, cracking and
phase inversion.
2. Creaming:
a. In an O/W emulsion, oil is the internal phase and water is the external
phase.
b. Oil has lesser density than water and the oil globules move up. This is called
up ward creaming in emulsions. Example: creaming in milk.
c. In a W/O emulsion, water is the internal phase and oil is the external phase.
d. Water has more density than oil and the water globules go down. This is
called down ward creaming in emulsions.
e. Rate of creaming can be explained using Stoke’s equation.
h/t = speed of creaming
η= viscosity of external
phase
d = particle diameter
G = acceleration due
to gravity
f. Creaming depends on globule size, viscosity of emulsion and difference in
density between oil and water.
g. Creaming will be slow with smaller size globules.
h. If the difference in density between water and oil is more, creaming will be
more. If oil and water has same density, then there will be no creaming at all.
i. If the viscosity of the emulsion is more, creaming will be slow.
3. Coalescence: The globules come together and merge to form bigger
globules. This phenomenon is called coalescence.
4. Cracking or breaking of emulsion:
a. It is the separation of oil and water into two layers. It can be due to a
number of reasons.
b. If an emulgent of opposite type is added, emulsion will break or crack. For
example: if calcium sterate is added to an emulsion containing potassium
sterate as an emulgent, cracking will take place. This is because, sodium
sterate forms o/w emulsion whereas calcium sterate forms w/o emulsion.

c. If the emulgent is decomposed, the emulsion will crack. Example: alkali
soaps (emulgent) are decomposed by acids. If any acid is added to the
emulsion, the emulsion will break immediately.
d. Gums, gelatin, and casein (emulgents) are insoluble in alcohol and if alcohol
is added to emulsions containing these emulgents, the emulgents will
precipitate out and the emulsion will break.
e. If we add a common solvent for oil, water and emulgent to the emulsion, we
will get a solution. Example: if we add alcohol to an emulsion containing
castor oil, water and soft soap, we will get a solution.
f. Microbes destroy the emulgent and cracking of emulsion occurs. Hence an
emulgent is necessary.
g. If the internal phase concentration exceeds 74 %, cracking of emulsion may
take place.
5. Phase inversion:
a. When an o/w emulsion gets converted into a w/o emulsion, it is called
phase inversion.
b. The type of emulsion formed depends on the solubility of emulgent. If the
emulgent is soluble in water, we will get o/w emulsion. If the emulgent is
soluble in oil we will get w/o emulsion.
c. For example: if calcium stearate is added to an emulsion containing sodium
sterate as an emulgent, phase inversion or cracking will take place. This is
because, sodium sterate forms o/w emulsion where as calcium sterate
forms w/o emulsion.
d. Another reason for phase inversion is concentration of internal phase. If
internal phase concentration changes, phase inversion occurs.

Evaluation of stability of emulsions:
1. Stability of emulsions can be evaluated by microscopy, extent of phase
separation, centrifugation and freeze thawing method.
2. Microscopy: In this method, the size of 100 globules is measured by using an
eye piece micrometer. The average size and standard deviation is calculated.
The smaller the average size, the better the emulsion. This is because,
creaming will be less with smaller globules. If standard deviation is less, it
indicates that the globules are uniform in size.
3. Extent of phase separation: In this method, the emulsion is taken in a
measuring cylinder and allowed to stand for 24 hours. The amount of external
phase separated is measured. The lesser the external phase separated, the
better the stability of the emulsion. If creaming does not take place at all, the
external phase separated will be zero. In the below example, emulsion B is
stable than A.
4. Centrifugation method: In this method the emulsion is centrifuged at high
speeds for one to two minutes. The amount of external phase separated is
measured. The lesser the external phase separated, the better the stability of
the emulsion. The stability of the emulsion can be known in less than five
minutes.
5. Freeze- thawing method: In this method, the emulsion is exposed to 40 and 4
degree centigrade alternatively for two hours. Then emulsion globule size
changes and phase separation are measured. Emulsions are good if they can
withstand these tests.

Advantages of emulsions:
1. Oily drugs can be taken in form of emulsions.
2. We can flavor the external aqueous phase easily.
3. Rate of absorption of oil in GIT is increased.
4. Two in compatible drugs can be included in one product. One drug can be
dissolved in oil phase and another in aqueous phase.
Disadvantages of emulsions:
1. It is difficult to prepare emulsions.
2. It has to be shaken well before use.
3. It has less stability when compared with syrups and elixirs.
4. It has stability problems like creaming, cracking and phase inversion.

Introduction:
Suspensions
1. A suspension contains fine solid drug particles dispersed in a solvent.
Example: Digene suspension, Gelusil suspension, Paracetamol suspension.
When a drug has less solubility in water, a suspension is prepared.
2. Example: Paracetamol has a solubility of 1.5 g in 100 ml water.
3. A paracetamol suspension has 5 g paracetamol in 100 ml. In this
suspension,
4. 1.5 g will be in dissolved state and the other 3.5 g will be in un dissolved state.
Properties of a good suspension:
Settling of drug particles in a suspension should be slow. After shaking, the
drug should stay in suspension for sufficient time to take a dose.
When suspensions are stored in a shelf, drug particles settle and form
sediment at the bottom. It should be easy to re disperse the sediment.
It should be easily pour able to take a dose.
It should have an elegant appearance.
It should have small drug particles (less than 100 micro meters).
Types of suspensions:
Suspensions containing diffusible solids
Suspensions containing in diffusible solids
Suspensions containing poorly wettable solids
Suspensions produced by chemical reaction
Colloidal suspensions
Deflocculated suspensions
Flocculated suspensions
Suspensions containing diffusible solids:
1. Some drugs are light and easily wettable. They readily mix with water and
on shaking form a homogenous suspension. The drug remains suspended
for sufficient time to take a dose. These drugs are called diffusible solids.
2. Example of diffusible solids: calcium carbonate, light magnesium carbonate,
magnesium trisilicate, light kaolin.
3. General method of preparation:
a. Triturate the powders in a mortar to get a fine powder.
b. Weigh the fine powders accurately and mix them in a mortar by
geometric dilution method.

c. Add enough vehicle and mix to produce a smooth dispersion without any
lumps.
d. Now dilute with vehicle until pourable. Transfer the suspension to a
measuring cylinder. Rinse the mortar, beaker and make up the
suspension to volume.
Suspensions containing in diffusible solids:
1. Some drugs settle very rapidly in a suspension. They will not give us
sufficient time to take a dose. Such drugs are called in diffusible solids.
Example: Aspirin, sulphadimidine, calamine, zinc oxide.
2. We can solve this problem by using thickening agents in the suspension.
The thickening agent like acacia, tragacanth, xanthan gum, sodium carboxy
methyl cellulose increase the viscosity of the suspension. Hence settling of
drugs will be slow and it will be convenient to take a dose.
a. Prepare the vehicle containing thickening agent, preservative, flavoring
agent, and coloring agent using a mortar.
b. Add the above vehicle to the mortar containing drug powders and mix to
get a smooth dispersion without any lumps.
c. Now dilute with vehicle until pourable, transfer to a measuring cylinder
and make up to volume.
Suspensions containing poorly wettable solids:
1. Some drugs are poorly wetted by water. It is difficult to prepare suspensions
using such drugs. They will form lumps and foam on shaking with water.
Example: Salicylic acid.
2. We can solve this problem by use of wetting agents in the suspension.
Examples: alcohol, glycerol, tweens.
a. Prepare the vehicle containing wetting agent, thickening agent,
preservative, flavoring agent, and coloring agent using a mortar. Add this
vehicle to the mortar containing drug powders and mix to get a smooth
dispersion without any lumps.
b. Now dilute with vehicle until pourable, and transfer to a measuring cylinder
and make up to volume.

Suspensions produced by chemical reaction:
1. These suspensions are produced by a chemical reaction.
2. Dilute solutions of the reactants are mixed and we get a suspension of
diffusible solids. Example: zinc sulphide lotion B.P.C.
3. Dissolve sulphurated potash in 40 ml of water.
4. Dissolve zinc sulphate in 40 ml of water.
5. Add sulphurated potash solution to zinc sulphate solution with constant
stirring.
6. Transfer to a measuring cylinder and make up to volume.
Colloidal dispersions or suspensions:
1. These suspensions contain the solid drug particles of colloidal range
(1 – 1000 nm). The drug particles are very small and do not settle in a
suspension.
2. Example: Milk of magnesia or magnesium hydroxide mixture or cream of
magnesia.
3. Example: Aluminum hydroxide gel, aluminum phosphate gel.
4. Milk of magnesia preparation method:
a. It is prepared by chemical reaction method, that is, hydration and
precipitation method.
b. The two chemical reactions involved are
c. Precipitation reaction: MgSO4 + NaOH = Mg(OH)2 + Na2SO4
d. Hydration reaction: MgO + H2O = Mg(OH)2
e. In this method, a solution of sodium hydroxide is triturated with light
magnesium oxide to form a smooth cream; this is diluted and added
slowly to a solution of magnesium sulfate. Dilute solutions are used to
get a very fine precipitate of magnesium hydroxide.
f. 48 hrs is required for the hydration reaction to be completed.
g. After the magnesium hydroxide is settled, the supernant liquid is
decanted and the precipitate is washed with purified water until it is free
of sodium sulphate.
h. The precipitate is then mixed with purified water and made up to volume.
i. If hydration method is used alone, we get a very viscous product which is
not pourable.
j. By precipitation reaction method we get magnesium hydroxide particles
which settle quickly.

k. Hence, this suspension is made by two reactions, so that a
product with optimum viscosity is obtained. The drug particles
do not settle quickly and a dose can be taken after shaking.
Deflocculated and flocculated suspensions: The below table
gives the differences between a flocculated and deflocculated
suspensions.
S.NO Deflocculated Flocculated
1 The drug particles exist
independently
The drug particles form loose
aggregates called flocs.
2 Particles settle slowly Flocs settle rapidly
3 Hard cake is formed at the
bottom
A loose cake is formed at the bottom.
4 Difficult to re disperse the cake Easy to re disperse the cake.
5 Supernant is cloudy Supernant is clear
6 Good appearance Appearance not good
7 Suspending agents are required
to prepare.
Flocculating agent is required.

Formulation additives used in suspensions: The different ingredients
required for a suspension are given in below table.
S.NO Ingredient Purpose Example
1 Drug It gives medicinal action Paracetamol
2 Wetting agent To wet the drug particles with
vehicle
Tweens, alcohol,
glycerol
3 Flocculating
agents
To prepare flocculated
suspension
Xanthan gum,
electrolytes
4 Thickening
agents
To increase viscosity of
suspension and reduce
settling of drug particles
Tragacanth,
xanthan gum,
sodium CMC
5 Buffers To adjust pH of suspension for
good stability
Citric acid and
sodium citrate
6 Coloring agents To give a color to suspension Amaranth red,
sunset yellow
7 Sweetening
agents
To give a sweet taste to
suspension
Sugar
8 Flavor To give a pleasant flavor to
suspension
Peppermint flavor,
Pineapple flavor
9 Preservative To prevent microbial growth Sodium benzoate
10 Solvent Vehicle Purified water
Stability problems in suspensions:
1. The stability problem with suspensions is settling of drug particles
and ease of re dispersibility.
2. When settling of drug particles occurs in a suspension very fast, it
will be difficult to take a dose.
3. Settling depends on the size of drug particles and viscosity of the
vehicle.
4. Speed of settling can be explained using Stoke’s equation. It is given
below.

h = height of settling
liquid,
t = time taken for settling
d = particle diameter
h/t = speed of settling
η= viscosity of liquid
G = acceleration due to
gravity
5. Speed of settling is directly proportional to square of particle diameter.
If the particle size is doubled, speed of settling increases by 4 times.
6. Speed of settling is directly proportional to density difference between
solid drug particles and liquid. Greater the difference in density, greater
is the settling of drug particles.
7. Speed of settling is inversely proportional to viscosity of liquid. If
viscosity is doubled, speed of settling becomes half.
8. Hence, by reducing drug particle size and increasing viscosity of liquid,
we can reduce settling speed in suspensions.
9. Bigger drug particles settle quickly. Hence use smaller drug
particles to avoid the problem of settling.
10. Settling of drug particles will be slow in viscous vehicles. Hence
use thickening agents like tragacanth, acacia, sodium carboxy
methyl cellulose and xanthan gum. They increase the viscosity of the
suspension and reduce settling of drug particles.
11. On long standing for two or three months a hard cake will
form in a suspension which is very difficult to re disperse. This can
be prevented by preparing a flocculated suspension.
12. A flocculated suspension contains loose aggregates of drug
particles called flocs. They settle quickly, but form a loose cake at the
bottom which is easy to redisperse.
13. Hence by preparing a flocculated suspension we can avoid the
stability problems in suspensions.

Evaluation of stability of suspensions:
1. Sedimentation parameters are used to evaluate stability of suspensions.
2. They are sedimentation volume (F) and degree of flocculation (β).
3. Sedimentation volume = F = Vu / V0.
4. V0 = Initial volume of sediment, Vu = Ultimate or final volume of
sediment.
5. Example: A 50 ml suspension on standing for one day has an ultimate
sediment volume of 10 ml. F = 10/50 = 0.2.
6. Example: A 50 ml suspension on standing for one day has an ultimate
sediment volume of 40 ml. F = 40/50 = 0.8.
7. So, if F value is more, it indicates that it is a stable suspension. F value
is between 0 to 1. The best suspension will have a F value of 1.
8. Degree of flocculation: This is used to have an idea of the extent of
flocculation in a suspension.
9. A flocculated and deflocculated suspension is prepared and taken in the
measuring cylinder as shown in the below figure.
10. Degree of flocculation = β = Fflocculated suspension / Fdeflocculated suspension.
11. Example: The F values of deflocculated and flocculated suspensions
are 0.2 and 0.8. Then β = 0.8 / 0.2 = 4. This indicates that the sediment
volume is 4 times more in flocculated suspension. Greater the degree of
flocculation value, better the flocculated suspension. If β = 1, it indicates
that there is no flocculation.
Deflocculated suspension Flocculated suspension

Advantages of suspensions:
1. If drug is insoluble in water, we have to prepare a suspension.
Example: Paracetamol suspension.
2. If drug is having bad taste and smell, it is better to prepare a
suspension. Example: Chloramphenicol palmitate. If drug is in
undissolved form, it will not dissolve in mouth and we will not know
the taste of drug.
3. Bioavailability of suspensions is greater than tablets and capsules.
4. Long acting injections are made as suspensions. The drug
particles will slowly dissolve in the muscle and release the drug for
long period of time.
Disadvantages of suspensions:
1. Settling of drug particles take place in suspensions.
2. Exact dose cannot be taken because of settling of drug particles.
3. Bioavailability is less than syrups and elixirs.

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