LIQUID PREPARATIONS

Mr. Sakala BSc Pharmacy

2023
 Definition:
What are liquid dosage forms?
These are pharmaceutical preparations which
involve a mixture of active drug components and
non-drug components ) excipients) and are
prepared by dissolving the active drug in an
aqueous or non-aqueous solvent (eg glycerine,
ether, alcohol,) by suspending the drug in
appropriate medium or by incorporating the
drug substance into an oil or water phase e.g
suspensions, emulsions, syrups, elixers.
TYPES OF LIQUID DOSAGE FORMS
SOLUTIONS
What is a solution?
Definition:
 A solution is a homogeneous, molecular, mixture
of two or more components.
 Homogenous One-phase Transparent system
consisting of two or more components.
 The components do not separate on standing
 The components cannot be separated by
filtration.
 These are prepared by dissolving the active
ingredient(s) in a solvent/ suitable vehicle.
 The simplest solution consists of two
components, a solute dissolved in a solvent.
 The solute and the solvent could be in the
solid, liquid or gaseous states of matter.
 Solutions can be prepared by simple mixing
of the solutes with the solvent system.
 In industry, solutions are prepared in large
mixing vessels which are thermostatically
controlled should a specific temperature be
desired.
 CLASSIFICATION OF SOLUTIONS

Based on vehicle used

A. Aqueous B. Sweet C. Nonaqueous

1.Douches &/or Viscid 1.Elixirs
2.Enemas 1.Syrups 2.Spirits
3.Gargles 2.Honeys 3.Collodions
4.Mouthwashes 3.Mucilages 4.Glycerins
5.Nasal washes 4.Jellies 5.Lotions
6.Juices 6.Liniments
7.Sprays 7.OleoVitamin
8.Otic solutions
9.Inhalations
Based on Purpose

Oral In mouth &

1.Syrups throat
2.Elixirs 1.Mouth washes
3.Spirits 2.Gargles
4.Linctuses
3.Throat paint
5.Drops
6.Draughts 4.Throat sprays
On body Surfaces In body
1.Collodions Cavities
2.Lotions 1.Douches
3.Liniments 2.Enemas
3.Ear drops,
4.Nasal sprays
What are the components of
a solution?
Components of a solution
1. The solvent system
2. The drug
3. The excipients
1. The solvent system
i. Aqueous solvents
 Most pharmaceutical solutions are water
based.
 Water is the most commonly used solvent
due to its many advantages, such as;
> its lack of toxicity
> and low cost.
 Different types of water have been defined
in the BP and USP
 Tap (drinking) water is not normally used or
the manufacture of pharmaceutical solutions
or for extemporaneous compounding.
 Tap water is there fore purified, for example;
i. by distillation
ii. ion exchange or
iii. reverse osmosis to produce Purified
Water.
 Purified water = Non-parenteral solutions
 Water for injection = Parenteral solutions
 Co-solvents
 On its own, water does not dissolve
many drug compounds to a sufficient
degree to enable the preparation of a
pharmaceutical solution.
 Toenhance solubility, co-solvents are
added.
 Commonly used examples include
glycerol, propylene glycol, ethanol and
poly(ethylene glycol), glycerine,
glycofural etc
 Use of co-solvents is limited by;
i. their toxicity
ii. drug solubility in the formulation
and
iii. cost
Non-aqueous solvents
 These are used when the drug is
insufficiently soluble or stable in aqueous
systems, or when a solution is intended for
specific properties, such as sustained drug
absorption.
 They are limited to certain delivery routes,
such as intramuscular and topical, due to
their;
i. Unpalatability
ii. Toxicity
iii. Irritancy or
iv. Immiscibility with physiological fluids
 From the vast number, most
organic liquids are toxic.
 These liquids are used as co-
solvents with water, as co-solvents
with other organic liquids, or on
their own.
Reading Assignment.
1. Write short nots on the types of water
and their uses as defined in the BP and other
pharmacopoeias.
2. Write short nots on the commonly used
organic liquids and their uses.
2 pages + a cover and references pages
Font type and size: Times New Roman 12,
Century Gothic 11
2. The drug
 This could be a small molecule (eg aspirin), a
large bio-therapeutic molecule (eg insulin) or
an antibody.
 The drug is present as molecules or ions
throughout the solvent.
 It is usual to ensure that the drug
concentration in a pharmaceutical solution is
well below its saturation solubility in order to
avoid the possibility of drug precipitating out
of the solvent as a result of subsequent
temperature changes during. storage and use
3. The excipients
 Excipients – substances other than the drug or
prodrug which are included in pharmaceutical
solutions.
 They are used for a number of reasons such as;
 To enhance product stability
 To enhance bioavailability
 To enhance patient acceptability
 To aid product manufacture and
 For purposes of identification.
 Each excipient has a clear role in the product,
thus, the nature of an excipient used depends
on the requirements of the pharmaceutical
product.
 Some properties of excipients used in solutions
are;
 It should be non-toxic
 It should be non-sensitizing,
 It should be non-irritating
 It should be compatible with all the other
components of the formulation.
 Will look at specifics later:
 The route of administration is important.

 Many excipients are acceptable by certain, but

NOT ALL routes.

 For example, the preservative benzalkonium

chloride is used in oral, but not nebulizer,
solutions, as it causes bronchoconstriction.

 Like the drug, excipients could be small (e.g.

sucrose) or large (e.g. hydroxypropyl
methylcellulose) molecules.
TYPES OF SOLUTIONS
1. Solid solution-The solvent is solid
(a). Solid in solid eg Cu+ gold=12 karat yellow
gold
(b). Liquid in solid eg Hg dissolved in Ag
=Almagam
©. Gas in Solid eg Air dissolved in soap=froathing
soap
2. Liquid solution-solvent is liquid
(a). Solid in liquid eg salt in water
(b). Liquid in liquid eg alcohol in water
(c) Gases in liquid eg carbonated beverages

3. Gaseous solutions-the solvent is gas

(a). Solid in gas eg salfur in air
(b). Liquid in gas eg water vapour in air
( c). Gas in gas eg oxygenated air
SOLUBILITY
 Definition: Number of parts of solvent (by volume) that
will dissolve one part of solute (by weight of a solid or
liquid).
 The amount of a solute that passes into solution (per
ml).
 A solute will dissolve best in a solvent that has a similar
polarity to itself.
 •MISCIBILITY: when the two components forming a
solution are either both gases, solids or liquids it is
more usual to talk in terms of miscibility rather than
solubility.
 E.g. water and alcohol
 Immiscible: two liquids do not mix e.g. water and oil
 Factors Affecting Solubility of Solute
 1. Particle size – an increase in surface area to the solvent will increase
rate of solution. So the particle size should be reduced by comminution
before it is dissolved.
 2. Agitation – increases the rate of solution by removing from the surface
of the solute.
 3. Temperature-- heating a liquid also causes solubility to take place
more rapidly by increasing the frequency which solvent molecules collide
with the surface of the dissolving mixture.
 Exothermic reaction-The process of solution were heat is applied and
absorption of the heat takes place in the solutes, this increase in
temperature will cause more solute to go into solution
 Exothermic reaction – solute gives off heat during the process of
solution; solubility is decreased with an increase in temperature.
Example: more soluble in cold than hot water methyl cellulose and
calcium salts such as Ca(OH)2.
 4. pH – Many of the organic substances which are used medicinally are
either weak acids or weak bases. And their aqueous solubility depend
upon the pH of the solvent
 Advantages of solutions
1) Easier to swallow therefore easier for:
children - old age - unconscious people.
2) More quickly effective than tablets and
capsules. as drug become available
immediately for absorption
3) Homogenous therefore give uniform dose
than suspension or emulsion which need
shaking.
4) May be designed for any route of
administration
5) Flexible in achieving the proper dosing.
[Validate]
 6. Dilute irritant action of some drugs (aspirin, Kl, KBr)
hence minimize adverse effects in the GIT
7. Has fast absorption rate.
Disadvantages of solutions
 (1) Bulky therefore difficult to transport and store.
 (2) Unpleasant taste or odours are difficult to mask.
 (3) Has less accuracy. Needs an accurate spoon/ or any
other aid to measure the dose.
 (4) Technical accuracy needed to measure dose on
administration
 (5) Some drugs are poorly soluble
 (6) Less stable than solid dosage forms.
Major signs of instability: colour change, precipitation
microbial growth chemical gas formation.
 (7). Needs special storage and transferring
conditions.
 (8). Is easily infected by microorganisms.
METHODS OF PREPARING SOLUTIONS
(a) Simple Solution
(b) Solution by Chemical Reaction
(c) Solution by Extraction
1. Simple Solution

 Prepared by dissolving the solute in a suitable

solvent (by stirring or heating).
 Examples: Calcium hydroxide solution USP
(lime water),
 Some times the solvent may contain other
ingredients which stabilize or solubilize the
active ingredient
2. Solution by Chemical Reaction
Prepared by reacting two or more solutes with
each other in a suitable solvent For example,
Calcium lactate mixture is prepared by calcium
carbonate and lactic acid. Magnesium Citrate =
prepared by reacting official magnesium
carbonate with citric acid.

3. Solution by Extraction
Vegetable or animal origin are often extracted
with suitable solvent.
ADDITIVES IN SOLUTIONS
1-Preservatives
Solution may become contaminated for a number of
reasons:
1.Raw materials used in the manufacture of solutions are
excellent growth media for bacterial substances such as
gums, dispersing agents, sugars and flavors.
2.Equipment, environment and personnel contribute to
product contamination.
3.Consumer use may result in the introduction of
microorganism.
Preservative used should be:
1.effective against a wide spectrum
of microorganisms
2.stable for its shelf life
3.non toxic, non sensitizing
4.compatible with the ingredients in
the dosage form
5.free of taste and odour
ADDITIVES IN SOLUTIONS
1. Alcohols (Ethanol & Propylene glycol )
 Ethanol is useful as a preservative when it is used as a
solvent.
 It needs a relatively high concentration (> 10%) to be
effective.
 Propylene glycol preservative in the range of 15 to
30%.
 It is not volatile like ethanol.
Acids: (Benzoic acid & sorbic acid )
 They are used in a concentration range from 0.1 % to
0.5%.
 Only the non-ionized form is effective and therefore
its use is restricted to preparations with a pH below
4.5.
Esters: Esters (methyl, ethyl, propyl) of p-
hydroxybenzoic acid. hence called as methyl, ethyl,
propyl and butyl parabens)
 •They are employed at concentrations up to about
0.2%.
 •Effective and stable over a pH range of 4 to 8.
Quaternary Ammonium Compounds: Benzalkonium
chloride
 used at a relatively low concentration 0.002 to
0.02%.
 pH range of 4 to 10 and is quite stable at most
temperatures.
2-Antioxidants Vitamins, essential oils & almost
all fats and oils can be oxidized. Oxidation
reaction can be initiated by: 1. heat: maintain
oxidizable drugs in a cool place 2. light: use of
light- resistant container 3. heavy metals (e.g.
Fe, Cu): effect of trace metals can be
minimized by using citric acid or
ethylenediamine tetraacetic acid (EDTA) i.e.
sequestering agent . Antioxidants as propyl &
octyl esters of gallic acid, tocopherols or
vitamin E, sodium sulfite, ascorbic acid (vit. C)
can be used.
3-Sweetening agents
Sucrose is the most widely used
sweetening agent. Advantages: Colourless,
highly water soluble, stable over a wide
pH range (4-8), increase the viscosity,
masks both salty and bitter taste, has
soothing effect on throat. Polyhydric
alcohols (sorbitol, mannitol and glycerol)
possess sweetening power and can be used
for diabetic preparations.
4-Buffers:
To resist any change in pH 5-Isotonicity modifiers:
osmotic pressure
• Solutions for injection
• Application to mucous membrane
• Large-volume solutions for ophthalmic application
Most widely used isotonicity modifiers are: dextrose
and NaCl
5-Viscosity enhancement It is difficult for aqueous-
based topical solutions to remain on the skin or in the
eye (why?) therefore low concentrations of jelling
agents are added to increase the viscosity of the
product.
6-Flavours and perfumes:
Mask unpleasant taste or odour
Natural products: fruit juices, aromatic oil
(peppermint, lemon etc.)
Artificial perfumes are cheaper, more readily
available and more stable than natural products
A solution must retain its clarity, colour,
odour, taste and viscosity over its shelf
life.
 Both physical and chemical stability of
solutions in their containers is very
important.
Numeracy in solution formulation
1. How much solid would be required in order
to produce 500 ml of a 15 mg/10 ml solution?
2. If 30 mg of an ingredient was dissolved in 1.5
ml of solvent, what would be the strength of
the resulting solution expressed as mg/ml?
3. What weight of sodium bicarbonate (in
grams) would be required to make 150 ml of a 6
g/l solution?
4. How much solid would be required in order
to produce 50 ml of a 0.2% w/v solution?
5. Express 30g of dextrose in 600mL of solution as a
percentage, indicating w/w, w/v or v/v.
Let y grams be the weight of dextrose in 100mL.
6. What is the final concentration if 60mL of a 12% w/v
chlorhexidine solution is diluted to 120mL with water?
7. What volume of 1% w/v solution can be made from
75mL of 5% w/v solution?
8. What dose of antibiotic will be contained in a 5mL
spoonful when a bottle containing 5g of penicillin V is
reconstituted to give 200mL of syrup?
THE END