Pharmaceutical Solutions

Pharmaceutical Solutions
By: Abera J
Introduction
By: Abera J
Introduction…..Liquid DFs
• Solution
– Solutions are clear Liquid preparations containing one or
more AIs dissolved in a suitable vehicle.
• Suspension…..Solid in Liquid dispersion
– Liquid preparations containing one or more AIs suspended

in a suitable vehicle.
3 By: Abera J
Introduction…..Liquid DFs
• Emulsion…….Liquid in Liquid dispersion
– Emulsions are two phase system in which one liquid is dispersed
through out another liquid in the form of small droplets.
• Colloids
A system in which finely divided particles, which are 1 nm - 0.5 µm in
size, are dispersed within a continuous medium in a manner that
prevents them from being settled rapidly
By: Abera J
Pharmaceutical Solutions
• Are DFs prepared by dissolving the AIs in an aqueous or non
aqueous solvent
• Can be formulated for different ROA;
– Orally…….Syrups, elixirs
– In mouth and throat……..Mouth washes, gargles, throat sprays.
– In body cavities…….Douches, enemas, ear drops, nasal spray
– On body Surfaces………..Collodions, lotions
– Parenterals…………Small and large volume IV fluids
By: Abera J
Advantages of Solutions
– Easier to swallow therefore suitable for children, old age
– The therapeutic agent is dissolved in the formulation and
is therefore immediately available for absorption
– Homogenous……….therefore uniform dose might be given
than suspension or emulsion which need shaking
By: Abera J
Disadvantages of Solutions
– Bulky……therefore difficult to transport and store
– Unpleasant taste are difficult to mask
– Unsuitable for therapeutic agents that are chemically
unstable in the presence of water
– Unsuitable for poorly soluble therapeutic agents
By: Abera J
Formulation of pharmaceutical solutions
– Drug/API – Viscosity enhancers
– Solvent: - Water, Oil – Density modifiers
– Cosolvents if needed for – Antioxidants
solubility – Preservatives
– Buffer (for maintaining pH) – Colour, flavouring agents
– Isotonicity modifiers
By: Abera J
Additives used in solution…
Isotonicity modifiers
– Solutions for injection

– Application to mucous membrane
– Solutions for ophthalmic application
– Most widely used isotonicity modifiers are: dextrose & NaCl
– Isotonicity adjustments can only be made after the addition
of all other ingredients
By: Abera J
Viscosity enhancer
– It is difficult for aqueous-based topical solutions to remain on the
skin or in the eye
– The viscosity of the formulation must be sufficiently controlled in
order to ensure the accurate measurement of the volume to be
dispensed
– Increasing the viscosity of some formulations may increase the
palatability
By: Abera J
• The viscosity of pharmaceutical solutions can be increased by the
addition of:
– Non-ionic
• Cellulose derivatives, e.g. methylcellulose hydroxyethylcellulose,
hydroxypropylcellulose
• Polyvinylpyrrolidone
– Ionic hydrophilic polymers.
• Sodium carboxymethylcellulose (anionic)
• Sodium alginate (anionic).
By: Abera J
Density modifiers
• It is rarely necessary to control the density of solutions except when
formulating spinal anesthetics.
– Solutions of lower density than CSF will tend to rise after injection and
those of higher density will fall.
– The terms used to describe the density of injections in relation to that
of spinal fluid are isobaric, hypobaric and hyperbaric, meaning of
equal, lower and higher density, respectively.
By: Abera J
– Careful control both of the density of such injections and
the position of the Pt on the operating table will enable
precise control of the area to be anaesthetized.
– The most widely used material for density modification is
dextrose.
By: Abera J
Buffers
• Buffers are employed to control the pH of the formulated product and,
in so doing, optimize the physicochemical performance of the product
• pH control is performed:
– To maintain the solubility of the therapeutic agent in the formulated

product
– To enhance the stability of products in which the chemical stability
of the active agent is pH-dependent
By: Abera J
Examples of buffer salts used in pharmaceutical solutions include:
– Acetates (acetic acid and sodium acetate): 1-2%
– Citrates (citric acid and sodium citrate): 1-5%
– Phosphates (sodium phosphate and disodium phosphate):
0.8-2%.
By: Abera J
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 e.g. gums, sugars & flavors.
2. Equipment, environment and personnel contribute to product

contamination.
3. Consumer use may result in the introduction of microorganism.
 a preservative should be added to the product
16 By: Abera J
• Preservative used should be:
– Effective against a wide spectrum of MOs
– Stable for its shelf life
– Non-toxic
– Inert toward adsorbtion onto the container from the product
– Compatible with the ingredients in the DF
– Free of taste and odor
– Should be more on the undissociated form
17 By: Abera J
• A wide range of preservatives is available for use in pharmaceutical
solutions
– Benzoic acid and its salts (0.1–0.3%)
– Sorbic acid and its salts (0.05–0.2%)
– Alkyl esters of parahydroxybenzoic acid (0.001–0.2%).
• Usually a combination of two members of this series is employed in

pharmaceutical solutions typically methyl and propyl
parahydroxybenzoates (in a ratio of 9:1).
By: Abera J
Factors affecting preservative efficacy in pharmaceutical solutions
• The activity of a preservative is dependent on the correct form of the
preservative being available in the formulation at the required concentration
to inhibit microbial growth (MIC)
• Factors that directly affect the efficacy of preservatives in solutions include;
– The pH of the formulation
– The presence of micelles….. an aggregate of molecules in a colloidal

solution
– The presence of hydrophilic polymers
By: Abera J
pH of the formulation
• Acidic preservatives are affected by pH
• The antimicrobial properties are due to the unionised form of the

preservative
• Due to the ability of unionised form to diffuse across the outer
membrane of the MOs and eventually into the cytoplasm.
• The neutral conditions within the cytoplasm enable the preservative to
dissociate, leading to acidification of the cytoplasm and inhibition of
growth.
By: Abera J
• The preservative efficacies of
parabens and the phenolics are
generally not affected by formulation
pH (within a pH range between 4.0
and 8.0)
• Due to the high pKa of the organic
Structural formula for the
hydroxyl group parahydroxybenzoate esters (where R
refers to an alkyl group).
By: Abera J
The presence of micelles
• If the preservative exhibits lipophilic properties then partition of these
species into the micelle may occur, thereby decreasing the effective
concentration of preservative in solution.
• To correct this problem, the preservative concentration must be

increased
By: Abera J
The presence of hydrophilic polymers
• The free concentration of preservative in solution formulations is
reduced in the presence of hydrophilic polymers,
e.g. polyvinylpyrrolidone, methylcellulose.

• Due to the ability of the preservative to interact chemically
with the dissolved polymer.
By: Abera J
• In certain circumstances, the preservative may be
incompatible with hydrophilic polymers in the formulation
due to an electrostatic interaction.
• Cationic hydrophilic polymers should not be used with
acidic preservatives in oral solution formulations.
By: Abera J
Antioxidants
• Oxidation reaction can be initiated by: heat, light, or heavy
metals (e.g. Fe, Cu)
– To minimize the effect of heat maintain oxidizable drugs in a
cool place;
– Use of light- resistant containers to prevent oxidation due to
light;
– Effect of trace metals can be minimized by using citric acid or
ethylenediamine tetraacetic acid (EDTA); i.e. Sequestering agent
By: Abera J
• Antioxidants are;
• Compounds that exhibit higher oxidative potential than the

therapeutic agent or,
• Compounds that inhibit free radical-induced drug decomposition.
• Typically in aqueous solution antioxidants are oxidised in preference to

the therapeutic agent
• Both water-soluble and water-insoluble antioxidants are commercially

available
By: Abera J
• Water-soluble antioxidants include;
– Sodium sulphite, sodium metabisulphite, sodium

formaldehyde sulphoxylate and ascorbic acid
• Water-insoluble antioxidants include;
– Butylated hydroxytoluene (BHT), butylated hydroxyanisole

(BHA) and propyl gallate
By: Abera J
• Antioxidants are employed in low concentrations (<0.2% w/w)
• The concentration of antioxidant in the finished product is
markedly less than the initial concentration
– Due to oxidative degradation during manufacture of the DF.
By: Abera J
Sweetening agents
● Sucrose is the most widely used sweetening agent.
Advantages:
• Colorless
• 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
29 By: Abera J
• Polyhydric alcohols such as sorbitol, mannitol and glycerol, possess
sweetening power and can be included in preparations for diabetic use
• Artificial sweeteners such as sodium or calcium salts of saccharin can be
used;
• In conjunction with sugars and alcohols to enhance the degree of
sweetness, or
• On their own in formulations for Pts who must restrict their sugar intake
• They are intense sweeteners and should be used at a concentration <

0.2%
By: Abera J
Flavouring agent
• Mask unpleasant taste
• Natural flavouring agent: fruit juices, aromatic oil (e.g.

peppermint)
• Artificial flavouring agents are cheaper, more readily

available and more stable than natural products.
31 By: Abera J
• The four basic taste sensations are salty, sweet, bitter and sour.
• Flavours that may be used to mask a salty taste include:
• Butterscotch, apricot, peach, vanilla and wintergreen mint
• Flavours that may be used to mask a bitter taste include:
• Cherry, mint and anise
• Flavours that may be used to mask a sweet taste include:
• Vanilla, fruit and berry
By: Abera J
• Flavours that may be used to mask a sour taste include:
• Citrus flavours and raspberry
• Usually a combination of flavours is used to achieve the optimal

taste-masking property
• Flavour adjuncts (e.g. menthol, chloroform) may be added to oral
solution formulations
• Add flavour to the formulation and act to desensitize the taste
receptors
• Augment the taste-masking properties of conventional flavours
By: Abera J
Colours
• Are pharmaceutical ingredients that impart the preferred colour to the

formulation.
• When used in combination with flavours, the selected colour should
‘match’ the flavour of the formulation,
• e.g. green with mint-flavoured solutions, red for strawberry-flavoured
formulations.
• The inclusion of colours is not a prerequisite for all pharmaceutical
solutions
By: Abera J
• The presence of a strongly coloured degradation product, which
does not affect the use of the product, may occasionally be
masked by the use of a suitable colour
• It is essential to ensure that any colour chosen is acceptable in
the country in which the product is to be marketed
• There is a range of both natural and synthetic colours
By: Abera J
Natural colours are;
• More widely acceptable
• Classified into carotenoids, chlorophyll, anthocyanins, and a miscellaneous

group which includes riboflavines, caramel and extracts of beetroot.
Synthetic or 'coal tar' dyes
• Tend to give bright colours
• Are generally more stable than natural materials
• Are commonly the sodium salts of sulphonic acids, and therefore they may be
incompatible with cationic drugs.
By: Abera J
Solvents
Ethyl alcohol (ethanol, C2H5OH)
• Ethyl alcohol is the most widely used non-aqueous solvent
– Particularly for external application
• At concentrations >15% ethanol exhibits antimicrobial activity
• It is used orally or parenterally only at low concentrations,

usually as a cosolvent with water
By: Abera J
• Alcohol, USP, is 94.9% to 96.0% C2H5OH by volume (i.e., v/v) when
determined at 15.56°C
• Dehydrated Alcohol, USP, contains not less than 99.5% C2H5OH by

volume and is used when an essentially water-free alcohol is desired.
• If required for external use then industrial methylated spirit (IMS), is

usually included rather than the more expensive ethanol.
– Contains 5% methyl alcohol as a denaturant so it is too toxic for

internal use
By: Abera J
Additives….
Diluted alcohol, NF
• Diluted Alcohol, NF, is prepared by mixing equal volumes of
Alcohol, USP, and Purified Water, USP.
• The final volume of such mixtures is not the sum of the
individual volumes of the two components
• The final volume is generally about 3% less than what would
otherwise be expected
By: Abera J
Glycerin, USP (Glycerol)
• Is a clear viscous liquid with a sweet taste
• It is miscible with both water and alcohol
• As a solvent, it is comparable with alcohol
• But because of its viscosity, solutes are slowly soluble in it
unless it is rendered less viscous by heating.
• Glycerin has preservative qualities
• Can be used as cosolvent in conjunction with water or alcohol
• It is used in many internal preparations.
By: Abera J
Propylene glycol
– Used as a solvent in oral solutions and topical preparations.
– Can function as a preservative in conc > 15%

– Used in conjunction with water or glycerol as a cosolvent
– It is not volatile as ethanol
By: Abera J
Water
• Water is the solvent most widely used as a vehicle for
pharmaceutical products due to the low cost and low toxicity
• The preferred and most commonly used vehicle in solutions is
Purified Water USP
• The main methods used in the preparation of purified water
are distillation, ion exchange, and reverse osmosis
By: Abera J
Solutions taken orally
Aromatic Waters
• Aromatic waters are clear, aqueous solutions saturated with

volatile oils or other aromatic or volatile substances (e.g. Camphor)
• They are used principally as flavored vehicles
• Their odors and tastes are similar to those of the drugs or volatile
substances from which they are prepared
E.g. chloroform water, Camphor water, peppermint water and anise

water
43 By: Abera J
Solutions
Solutions taken orally…
taken orally…
Chloroform water
– Diluted chloroform water is prepared by mixing 1part of

double strength chloroform water (official formulae) and
1part of water.
• Use………..…preservative, flavor
By: Abera J
Solutions
Solutionstaken orally…
taken orally…
Camphor water
• Diluted camphor water is prepared by mixing 1part of concentrated

camphor water (official formulae) and 40 parts of water.
• Use…………..flavor, mild expectorant
•Concentrated Camphor Water, B.P

• Camphor ………....4 g
• Alcohol (90%)….. 60 ml
• Water, to ……….100 ml
By: Abera J
Stability oftaken
Solutions Aromatic
orally…Waters
• Aromatic water will deteriorate with time, therefore:
• Should be made in small quantities,
• Prepared aromatic waters should be freshly used.
• Protected from intense light and excessive heat by storing

• Exposure to such condition results in loose of some of their desirable
characteristics.
• Stored in air tight, light resistant containers.
• Since aromatic waters are saturated solutions, lowering the temperature
causes separation of the aromatic component, thus producing cloudiness
• If they become cloudy or otherwise deteriorate; they should be discarded.
• Deterioration may be due to volatilization, decomposition or MOs growth

46 By: Abera J
Solutions takenorally…
Dry mixtures for solution
• Dry powder or granule form for reconstitution with a prescribed
amount of purified water immediately before dispensing to the
Pt.
• Contains all of the formulative components
• Drug, flavorant, colorant, buffers, and others, except for the

solvent
By: Abera J
• Once reconstituted, the solution remains stable when stored
in the refrigerator for the labeled period, usually 7 to 14 days,
depending on the preparation.
• Examples of dry mixtures for solution are;
• Cloxacillin Sodium for Oral Solution
• Penicillin V Potassium for Oral Solution
• Potassium Chloride for Oral Solution
By: Abera J
Syrups
• Syrups are concentrated, viscous, aqueous solutions of a sugar or
sugar substitute with or without flavors and medicinal substances
• Can be classified into:

• Medicated syrup
• Eg. Diphenhydramine syrup

• Non-medicated syrup or flavoured syrup
By: Abera J
• Syrups are particularly effective in the administration of drugs
to youngsters;
• Their pleasant taste
• The fact that syrups contain little or no alcohol
By: Abera J
Solutions
Solutions taken orally… taken orally…
• Non-medicated syrup or Flavored syrup: which contains
aromatic or pleasantly flavored substances

• Used as flavoring and as a vehicle
E.g.. simple syrup, Invert syrup

• Simple syrup (syrup BP): 85 % w/v solution of sucrose in water
• Used to apply sugar coatings to tablets
By: Abera J
Components of syrups
• Most syrups contain the following components in addition to the
purified water and any medicinal agents present:
• The sugar, usually sucrose, or sugar substitute used to provide
sweetness and viscosity;
• Antimicrobial preservatives;
• Flavorants, and Colorants
• Also many types of syrups contain special solvents, solubilizing

agents, thickeners
By: Abera J
• A saturated solution may lead to crystallization of a part of
the sucrose under conditions of changing temperature
• Polyols (e.g. glycerin or sorbitol) may be added to;
• Retard crystallization of sucrose,
• Increase the solubility of added ingredients
53 By: Abera J
Preparation of Simple Syrup
• There are four methods;
• Solution with heat
• Solution by agitation
• Addition of sucrose to a liquid medication or flavored liquid
• Percolation
• The method of choice depends on the physical and chemical
characteristics of the substances
By: Abera J
Preparation of Simple Syrup…
a) Solution with heat
• This is the usual method of making syrups:
– In the absence of volatile agents,
– In the absence of heat labile substances
– When it is desirable to make the syrup rapidly.
By: Abera J
• Purified water is heated to 80-85°C, removed from its heat
source
• Sucrose is added with vigorous agitation
• Then, other required heat-stable components are added to

the hot syrup
• The mixture is allowed to cool, and its volume is adjusted to
the proper level by the addition of purified water
By: Abera J
• Excessive heating in the preparation of syrups must be
avoided to prevent inversion of sucrose
• Inversion occur, the sweetness of the syrup is altered
because invert sugar is sweeter than sucrose, and the
normally colorless syrup darkens
– Because of the effect of heat on the levulose portion of
the invert sugar.
By: Abera J
(b) Agitation without Heat
•This process is used when heat would cause loss of valuable volatile
constituents.
•On a small scale;
– Sucrose and other formulation ingredients are dissolved in purified
water by placing the ingredients in a vessel of greater capacity than
the volume of syrup to be prepared, allowing intense agitation
without spillage.
By: Abera J
• Huge glass-lined or stainless steel tanks with mechanical stirrers or
agitators are employed in large-scale preparation of syrups.
• When solid agents are to be added to a syrup,
– It is best to dissolve them in minimal amount of purified water and
incorporate the resulting solution into the syrup.
• This process is more time consuming than the use of heat, but the
product has maximum stability.
By: Abera J
c) Addition of sucrose to a liquid medication or flavored liquid
•Occasionally a medicated liquid, such as a tincture or fluid extract, is
employed as the source of medication
– Contain alcohol-soluble constituents
– If the alcohol-soluble components are desired medicinal agents,

some means of rendering them water soluble is employed
By: Abera J
• If the alcohol-soluble components are undesirable components of
the corresponding syrup
– They are generally removed by mixing the tincture or fluid extract
with water
– Allowing the mixture to stand until separation of the water-insoluble

agents is complete
– Filtering them from the mixture
– The sucrose is added to the filtrate

By: Abera J
(d) Percolation
•In the percolation method;
• Either purified water or the source of the medicinal component
is passed slowly through a bed of crystalline sucrose, thus
dissolving it and forming a syrup.
• Involves two separate procedures:
– First the preparation of the extractive of the drug and
– Then, the preparation of the syrup.
By: Abera J
• If necessary, a portion of the liquid is repassed through the
percolator to dissolve all of the sucrose.
• An example……….ipecac syrup
• Prepared by adding glycerin and syrup to an extractive of

powdered ipecac obtained by percolation
By: Abera J
• To be successful in using this process, technique is critical:
1. The percolator used should be cylindrical or semicylindrical
and cone-shaped as it nears the lower orifice;
2. A coarse granular sugar must be used, otherwise it

will coalesce into a compact mass, which the liquid
cannot permeate.
By: Abera J
Artificial Syrups (Non-Nutritive Syrups)

•Intended as substitutes for sucrose syrups and are to be
administered to persons who must regulate their sugar intake
accurately.
•Does not increase blood sugar level,

– For persons suffering from DM.
e.g. Diabetic Simple Syrup (6% cyclamate sodium and 0.6% saccharin Na)
By: Abera J
Reading Assignment
– Elixirs
– Linctuses
– Spirits
– Tinctures
– Solutions used in the mouth and throat
– Solutions instilled into body cavities
– Topical solutions
– Otic solutions
– Nasal solutions
By: Abera J
Parenteral Solutions
• Parenteral solutions are sterile, pyrogen-free preparations intended
to be administered parenterally.
• Injected directly into body ………….unique requirements
– Manufacturing (purity/sterility of components)
– Preparation and admixture (aseptic technique,…)
– Administration
By: Abera J
ParenteralSolutions…
Parenteral solutions
• Parenteral products are unique from any other type of pharmaceutical DF
for the following reasons
– All product must be sterile
– All products must be free from pyrogenic (endotoxin) contamination
– Injectable solutions must be free from visible particulate matter
– Products should be isotonic
By: Abera J
Parenteral Solutions…
Types of preparations for parenteral preparation
– Injection: are liquid preparations that are solutions there

of
• Eg, insulin injection
– For injection: dry solids that upon addition of suitable

vehicles yield solutions, eg. Cefuroxime for injection
– Injectable emulsion: liquid preparation of drug substance dissolved
or dispersed in a suitable emulsion medium,
• eg, propofol
By: Abera J
Types of preparations for injections…
– Injectable suspension: liquid preparation of solid suspended
in a suitable liquid medium.
– For injectable suspension: dry solid that upon addition of a
suitable vehicle yields injectable suspensions.
By: Abera J
Vehicles and added substances for injections
Water for injection, USP:

– Is intended for use in the preparation of parenteral solutions
and in the preparation of some bulk pharmaceutical chemicals
(in the large-scale manufacturer of injections).
– It must be protected from microbial contamination.
– It meets the requirements of all of the tests under purified

water + Bacterial Endotoxin Test.
By: Abera J
Sterile water for injection, USP
• It is prepared from water for injection that is sterilized and suitably
packaged
• It is packaged in single-dose containers not larger than 1L
• Must be pyrogen free but does have an allowable endotoxin level not
more than 0.25 USP endotoxin units per mL
• It contains no antimicrobial agent or other added substance.
• It is used as diluents for parenteral products
• Bacterial Endotoxin Test + Particulate Matter Test

By: Abera J
Bacteriostatic water for injection, USP:
– Is sterile water for injection which contain one or more
suitable antimicrobial agents.
– It is intended to be used as diluent for parenteral
products.
– It is packaged in single or multiple-dose containers (vials),
not larger than 30mL size
By: Abera J
Sodium chloride injection, USP
– Is a sterile isotonic solution of sodium chloride in water for injection
– May be used as a sterile vehicle in solutions or suspensions of drugs
for parentral administration
– Contain no antimicrobial agent
Bacteriostatic Sodium chloride injection, USP
– Is a sterile isotonic solution of sodium chloride in water for injection.
– Contains one or more suitable antimicrobial agents.
By: Abera J
Ringer’s injection, USP
– Is a sterile solution containing NaCl, KCl, and CaCl2 in

water for injection.
– The three agents are present in concentrations similar to
those of physiological fluids.
– Used as a vehicle and as an electrolyte replenisher and
plasma volume expander
By: Abera J
Non-aqueous vehicles
– Are sometimes used when there are limited water solubility of
drugs or susceptibility to hydrolysis.
– Fixed vegetable oils like corn oil, cottonseed oil, peanut oil, and
sesame oil,
• But not mineral oil or paraffin b/c not absorbed by body
tissues
•PEG, glycerol, propyl glycol, alcohol
By: Abera J
Other Additives
– Suitable substances may be added to preparations intended for
injection to increase stability or usefulness
• Antimicrobial preservatives, buffers, solubilizers, antioxidants,
– Special care should be taken in the choice and use of additives in
preparations for injection that are administered in a volume
exceeding 5ml
By: Abera J
– Antimicrobials must be added to preparations intended for
injection that are packaged in multiple-dose containers
• The AIs may have antimicrobial activity
– Such substances also meet the requirements of antimicrobial

preservatives-effectiveness
– The air in the container may be evacuated or be displaced by a
chemically inert gas if the article sensitive to oxygen.
By: Abera J
Small-volume intravenous injection
•Is applied to an injection that is packaged in containers
labeled as containing 100mL or less.
Example
– furosemide injection (Lasix R)
– Oxytocin injection
By: Abera J
Large-volume intravenous solution:
– is a single dose injection that is intended for IV use and is packaged in
container labeled as containing more than 100 mL.
– IV infusions
Examples,
– dextrose injection, USP : 2.5, 5, 10, 10, 40% dextrose
– Sodium chloride injection, USP (NS)
– Dextrose and Sodium chloride injection, USP (DNS)
– Ringer’s injection, USP
•NS, dextrose, Ringer etc. can be used for reconstituting/diluting parenterals.
By: Abera J
By: Abera J

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Pharmaceutical Solutions

– Liquid preparations containing one or more AIs suspended

– In mouth and throat……..Mouth washes, gargles, throat sprays.

– In body cavities…….Douches, enemas, ear drops, nasal spray

– On body Surfaces………..Collodions, lotions

– Parenterals…………Small and large volume IV fluids

– Easier to swallow therefore suitable for children, old age

– The therapeutic agent is dissolved in the formulation and

is therefore immediately available for absorption

– Homogenous……….therefore uniform dose might be given

than suspension or emulsion which need shaking

– Bulky……therefore difficult to transport and store

– Unpleasant taste are difficult to mask

– Unsuitable for therapeutic agents that are chemically

unstable in the presence of water

– Unsuitable for poorly soluble therapeutic agents

– Drug/API – Viscosity enhancers

– Solvent: - Water, Oil – Density modifiers

– Cosolvents if needed for – Antioxidants

– Buffer (for maintaining pH) – Colour, flavouring agents

– Solutions for injection

• It is rarely necessary to control the density of solutions except when

formulating spinal anesthetics.

those of higher density will fall.

– The terms used to describe the density of injections in relation to that

of spinal fluid are isobaric, hypobaric and hyperbaric, meaning of

equal, lower and higher density, respectively.

the position of the Pt on the operating table will enable

precise control of the area to be anaesthetized.

– The most widely used material for density modification is

– To maintain the solubility of the therapeutic agent in the formulated

– Acetates (acetic acid and sodium acetate): 1-2%

– Citrates (citric acid and sodium citrate): 1-5%

– Phosphates (sodium phosphate and disodium phosphate):

Solution may become contaminated for a number of reasons;

1. Raw materials used in the manufacture of solutions are excellent growth

2. Equipment, environment and personnel contribute to product

3. Consumer use may result in the introduction of microorganism.

 a preservative should be added to the product

– Effective against a wide spectrum of MOs

– Stable for its shelf life

– Inert toward adsorbtion onto the container from the product

– Compatible with the ingredients in the DF

– Free of taste and odor

– Should be more on the undissociated form

– Sorbic acid and its salts (0.05–0.2%)

– Alkyl esters of parahydroxybenzoic acid (0.001–0.2%).

• Usually a combination of two members of this series is employed in

– The presence of micelles….. an aggregate of molecules in a colloidal

• The antimicrobial properties are due to the unionised form of the

• To correct this problem, the preservative concentration must be

e.g. polyvinylpyrrolidone, methylcellulose.

• Compounds that exhibit higher oxidative potential than the

• Compounds that inhibit free radical-induced drug decomposition.

• Typically in aqueous solution antioxidants are oxidised in preference to

• Both water-soluble and water-insoluble antioxidants are commercially

– Sodium sulphite, sodium metabisulphite, sodium

– Butylated hydroxytoluene (BHT), butylated hydroxyanisole

• Antioxidants are employed in low concentrations (<0.2% w/w)

• The concentration of antioxidant in the finished product is

markedly less than the initial concentration

– Due to oxidative degradation during manufacture of the DF.

• They are intense sweeteners and should be used at a concentration <