Pharmaceutical solutions

Session objective
At the end of this session, students will be able
to:
• Understand the different types of solution dosage
forms and develop skills to compound them
 Presentation Outline
 Introduction
 Formulation of pharmaceutical solutions (API and
Excipients)
 Solutions taken orally
 Solutions used in the mouth and throat
 Solutions instilled into body cavities
 Topical solutions
 Injectables (sterile products)
 General methods of preparation
 Introduction
 A solution is a homogenous mixture that is prepared
by dissolving a solid, liquid, or gas in another liquid.

 It represents preparations in which the solute

molecules are dispersed among those of the solvent.

 Most solutions are unsaturated with the solute,

 i.e., concentration of solute in the solution is
below its solubility limit.
 The strengths of pharmaceutical solutions are usually
expressed in % strength.
 Introduction (cont’d)

 Solutions may be classified on the basis of site of

administration and composition than by
physicochemical definitions.
 For instance, pharmaceutical solutions may be
classified as:
 oral solution,
 otic solution,
 ophthalmic solution
 nasal solutions
 topical solution.
 Injectable solutions
 Introduction (cont’d)

Advantages of solution dosage forms:

 Easier to swallow than solids
 particularly acceptable for pediatric and
geriatrics
 Therapeutic response of the drug is faster from
solutions than solid dosage forms.
 Uniform dosing is possible.
 Minimized irritation effect of some drugs (e.g.,
aspirin, KCl,)
Solution dilutes immediately with gastric fluid
 Introduction (cont’d)

Disadvantages of solution dosage forms:

 Bulky and inconvenient to transport and store
 Stability of ingredients in aqueous solution is often
poorer than if formulated as a tablet or capsule,
(particularly if they are susceptible to hydrolysis).
 May support microbial growth and hence require
preservatives.
 Bad taste of drugs can be felt.
 Formulation of solutions
 Solution formulations = Excipients + API(s)
 Excipients) such as:
 Solvents
 Sweetening agents
 Flavours and colours
 Preservatives
 Buffers
 Density modifiers
 Tonicity modifiers
 Viscosity enhancement
 Stabilizers and antioxidants
 Solvents
Aqueous solutions
 Water is the solvent most widely used as a vehicle for
pharmaceutical products, because of its physiological
compatibility, tasteless and lack of toxicity.
Types of pharmaceutical water
Potable water
 Is drinking water, drawn freshly from a main supply
 It should be palatable and safe for drinking
 Its chemical composition may include mineral impurities
which could react with drugs, e.g., the presence of calcium
carbonate in hard water
 Needs purification for pharmaceutical preparation
 Solvents (cont’d)
Purified water
 Freshly boiled & cooled potable water, normally
prepared by distillation or deionization of potable
water or by the process of reverse osmosis.
 Distilled water is purified water that has been
prepared by distillation.
Water for injection (WFI)
 Pyrogen-free distilled water, sterilized immediately
after collection and used for parenteral products.
 The European pharmacopoeia permits distillation as
the process for producing WFI.
 Sterile water for injection: sterilized WFI is used for
dissolving parenteral products.
 Solvents (cont’d)

Aromatic water
 Are near-saturated aqueous solution of volatile oils
or other aromatic or volatile substances, and are
often used as a vehicle in oral solutions.

 Although water is widely used for pharmaceutical

preparations, it may not be possible to ensure
complete solution of all ingredients at all normal
storage temperatures.
 Solvents (cont’d)

 For example, the solubility of a weak electrolyte or

non-polar compound in water can often be
improved by altering the polarity of the solvent.
 This can be achieved by the addition of another
solvent that is both miscible with water and in which
the compound is also soluble.
 Vehicles used in combination to increase the
solubility of a drug are called cosolvents.
 Solvents (cont’d)

 The choice of suitable cosolvents is somewhat

limited for pharmaceutical use because of possible
toxicity and irritancy.
 Ideally, suitable blends should possess values of
dielectric constant between 25 and 80.
 The most widely used system that will cover this
range is a water/ethanol blend.
 Other suitable solvents for use with water include
glycerol, propylene glycol and isopropyl alcohol
 Solvents (cont’d)

Non-aqueous solutions
 If the drug is not completely soluble in aqueous
solvent, or if it is unstable in aqueous systems, an
alternative, non-aqueous solvent is used.
 It is essential that, in choosing a suitable solvent, its
toxicity, irritancy, sensitizing potential, flammability,
cost, stability and compatibility with other excipients
are taken into account.
 Solvents (cont’d)

Fixed oils of vegetable origin

 These are non-volatile oils that consist mainly of fatty
acid esters of glycerol.
 For example, arachis oil, olive oil, sesame oil, maize
oil, cottonseed oil, soya oil and castor oil
Alcohols
 Ethyl alcohol (Ethanol) is the most widely used
solvent in this class.
 Ethanol, as solvent, is next in importance to water.
 Solvents (cont’d)

 Ethanol is widely used for its miscibility with water

and its ability to dissolve many water insoluble
ingredients.
 Ethanol is rarely used for internal preparations but is
useful solvent for external preparations.
 An advantage of ethanol is that growth of
microorganisms does not occur in solutions
containing alcohol in reasonable concentration (>
15%).
 Solvents (cont’d)

 In OTC products the USP limits ethanol content limit

of 0.5% for children under 6 years old.

 Products intended for children 6 to 12 years of age,

the recommended limit is 5%.

 For products recommended for children over 12

years of age and for adults, the recommended limit is
10%.
 Solvents (cont’d)

Glycerin
 Is an excellent solvent, although its range is not as
extensive as that of water or alcohol.
 It is viscous and miscible with both water and alcohol.
 It dissolves alkalies, salts, vegetable acids, pepsin,
tannin, and some active principles of plants, gums,
soluble carbohydrates, and starch.
 It may be added as a stabilizer and sweetener in
internal preparations.
 Solvents (cont’d)
Propylene glycol
 used as a substitute for glycerin, miscible with water
in all proportions.
 Less viscous liquid and a better solvent than glycerin.
 It dissolves many essential oils but immiscible with
fixed oils.
 It is as effective as ethanol in its power of inhibiting
mold growth and fermentation.
 act as preservative in the range of 15% to 30%.
 Solvents (cont’d)

Isopropyl alcohol
 Possesses solvent properties similar to those of
ethanol and is used instead of ethanol in a number of
pharmaceutical manufacturing operations.
 It has the advantage in that the commonly available
product contains not over 1% water, whereas
ethanol contains about 5% water, often a
disadvantage
 It is used in some liniment and lotion preparations.
 It should not be taken internally.
 Solvents (cont’d)

Dimethylsulphoxide (DMSO)
 This is a highly polar compound and is thought to aid
the penetration of drugs through the skin.
 used mainly as a solvent for veterinary drugs
Ethyl ether
 This material is widely used for the extraction of
crude drugs,
 But because of its own therapeutic activity it is not
used for the preparation of formulations for internal
use.
 It is, however, used as a cosolvent with alcohol in
some collodions.
 Solvents (cont’d)

 Liquid paraffin
 Often used as a solvent for the topical application of
drugs in emulsion formulations.
 Miscellaneous solvents
-Isopropyl myristate and isopropyl palmitate
(in cosmotics)
- Dimethylformamide and dimethylacetamide
(in veterinary formulations)
- xylene ( in ear drops)
 Buffers
 Resist any change in pH when an acid or an alkali be
added.
 The choice of suitable buffer depends on the pH and
buffering capacity required.
 Most pharmaceutically acceptable buffering systems
are based on carbonates, citrates, gluconates,
lactates, phosphates or tartrates.
 Borates can be used for external application, but not
to mucous membranes or to abraded skin.
 Buffers (cont’d)
 As the pH of most body fluids is 7.4, products such as
injections, eye drops and nasal drops should, in
theory, be buffered at this value to avoid irritation.
 Many body fluids themselves, however, have a
buffering capacity and, when formulating low volume
intravenous injections or eye drops, a wide pH range
can be tolerated.
 This is useful for a drug whose optimum stability,
solubility and absorption may depend on different
pHs.
 Tonicity modifiers
 Solutions for injection, for application to mucous
membranes, and large-volume solutions for
ophthalmic use must be made iso-osmotic with
tissue fluid to avoid pain and irritation.
 The most widely used tonicity modifiers are
dextrose and sodium chloride.
 Isotonicity adjustments can only be made after the
addition of all other ingredients, because each
ingredient will contribute to the overall osmotic
pressure of a solution.
 Viscosity enhancers
 Low viscous solutions will not remain in place on the
skin or eyes for any significant time.
 To counteract this effect, low concentrations of
gelling agents can be used to increase the apparent
viscosity of the product.
 For example, polyvinyl pyrolidone (povidone),
hydroxyethylcellulose, carbomer, etc.
 Preservatives
 Substances used in liquid & semisolids (preparations
which provide excellent growth media for microbes such
as syrups, emulsions, suspensions & creams) to prevent
growth of microorganisms.
 Certain hydroalcoholic & most alcoholic preparations
may not require the addition of a chemical preservative
when the alcoholic content is sufficient to prevent
microbial growth.
 In general, an alcohol content of 15% by weight in acid
solutions and 18% by weight in alkaline solutions is
sufficient to prevent microbial growth.
 Preservative (cont’d )
• Most alcohol containing preparations such as elixirs,
spirits, and tinctures are self-preserving and will not
require preservation.
• Syrups can be preserved by the maintenance of a high
concentration of sucrose as part of the formulation
(sucrose kills microorganisms by its osmotic effect).
 Preservatives (cont’d)
Examples of preservatives:
Acids (e.g., Benzoic acid, boric acid);
Alcohol (e.g., chlorobutanol);
Esters (e.g., methylparaben, ethylparaben,
propylparaben, buthylparaben)
Quaternary ammonium compounds (e.g.,
benzalkonium chloride)
 Phenols & chlorinated phenolic compounds
 Mercurials ( e.g., thiomersal)
 Preservatives (cont’d)
 When choosing a suitable preservative it must
be ensured that:
adsorption of the preservative onto the container
from the product does not occur,
its efficiency is not impaired by the pH of the
solution or by interactions with other ingredients.
 Density modifiers
 Density adjustment or modification is important in
formulating spinal anaesthetics.
 Solutions of lower density than cerebrospinal fluid
will tend to rise after injection and those of higher
density will fall.
 The most widely used material for density
modification is dextrose.
 Antioxidants
 The decomposition of pharmaceutical products by
oxidation can be controlled by antioxidants.
 Vitamins, essential oils, and almost all fats and oils
can be oxidized.
 Antioxidants: Ascorbic acid, Ascorbyl palmitate,
Butylated hydroxyanisole (BHA), Butylated
hydroxyltoluene (BHT), sodium metabisulfite
(Na2S2O5) etc.
 Sweetening agents
 Used to impart sweetness to a preparation
 Sucrose is traditionally the most widely used
sweetening agent.
 Mask the tastes of both salty and bitter drugs
 A comforting effect on the membranes of the
throat
• Disadvantage: Cariogenic , promotes dental
caries/plaque.
 Polyhydric alcohols: sorbitol, mannitol and glycerol
(lesser extent) are incorporated in preparations for
diabetic use.
 Sweetening agents (cont’d)
Artificial sweeteners
 Can be used in conjunction with sugars and alcohols
or by their own for patients who must restrict their
sugar intake.
 They are also termed intense sweeteners because
they are hundreds and even thousands of times
sweeter than sucrose.
 Only about six artificial sweeteners are permitted for
oral use within the European Union.
 Sweetening agents (cont’d)

 The most widely used being the sodium saccharin

and calcium saccharin.
 Less widely used are aspartame (E951), sodium
cyclamate (E952) and neohesperidine DC (E959).
 Flavours
 The simple use of sweetening agents may not be
sufficient to render palatable a product containing a
drug with a particularly unpleasant taste.
 In many cases, therefore, a flavouring agent can be
included.
 This is particularly useful in pediatric formulation to
ensure patient compliance.
 Types of flavoring agents

 Natural flavor: Anise oil, cinnamon oil, cocoa,

menthol, orange oil, peppermint oil, vanillin
 Artificial flavor: Any substance used to impart flavor
that is not derived from a spice or natural source
 Coloring agents
 After choosing a suitable flavor, it is often useful to
include a colour associated with that flavour in order
to:
 improve product attractiveness and
 enable easy product identification
 Types of coloring agents: natural and artificial.
 Natural:
 Example, Carotenoids, chlorophylls, saffron, red
beetroot extract, caramel & cochineal, iron oxide
 Coloring agents

 Saffron Caramel

 cochineal
 Coloring agents (cont’d)

 Artificial coloring agents:

- Amaranth ( also known as FD and C Red Number 2)
- Tertrazine
- Sunset yellow
- Coal tar dyes
- sodium salts of sulphonic acids
 Solutions taken orally

Oral solutions include:

 oral rehydration solutions,
 syrups,
 elixirs,
 spirits,
 oral tinctures
 Solutions taken orally…
Oral rehydration solutions
 Oral rehydration solutions are solutions taken orally
to replace rapid fluid loss (dehydration), associated
with diarrhea.
 A liter of typical oral rehydration solution contains 45
mEq Na+, 20 mEq K+, 35 mEq Cl−, 30 mEq citrate,
and 25 g dextrose.
 These formulation is available in liquid or powder
packet form for reconstitution.
 Solutions taken orally…
Syrups
• Syrups are concentrated sugar or sugar
substitute of aqueous preparations with or
without drug substances and flavoring agents.

• Most syrups contain a high proportion of

sucrose, usually 60% to 80%,
 Solutions taken orally…
Elixirs
 Elixirs are clear, sweetened hydroalcoholic solutions,
usually flavored to enhance their palatability.
 compared with syrups, less sweet and less viscous
because they contain a lower proportion of sugar.
 The proportion of alcohol in elixirs varies widely
because the individual components of the elixirs have
different water and alcohol solubility characteristics.
 For elixirs containing agents with poor water solubility,
the proportion of alcohol required is greater than for
elixirs prepared from components having good water
solubility.
 Solutions taken orally…
Spirits
 Spirits are alcoholic or hydroalcoholic solutions of
volatile substances, because of the greater solubility
of aromatic or volatile substances in alcohol.
 Generally, the alcoholic concentration of spirits is
usually over 60%.
 When taken orally, they are generally mixed with a
portion of water to reduce the pungency of the spirit.
 Spirits may also be applied externally, or used by
inhalation, depending upon the particular preparation.
 Depending on the materials, spirits may be prepared by
simple solution, solution by maceration, or distillation.
 Solutions taken orally…
Tinctures
 Tinctures are alcoholic or hydroalcoholic solutions
prepared from vegetable materials or from chemical
substances.
 They may contain alcohol in amounts ranging from
approximately 15% to 80%.
 The alcohol content protects against microbial growth
and keeps the alcohol-soluble extractives in solution.
 In addition to alcohol, other solvents, such as glycerin,
may be employed.
 Solutions used in the mouth and throat
Solutions used in the mouth
 A variety of medicinal substances are employed topically
in the mouth for a number of purposes:
 Topical anesthetic indicated for temporary relief of
pain, soreness, and irritation in the mouth,
 Dental anti-infective,
 Mouthwash/Gargle used primarily as a freshening
mouth cleanser
Solutions used in the throat
 are used for treatment of sore throat, throat
infections, and to neutralize acid reflux from stomach
to esophagus and throat
 Solutions instilled into body cavities
Ophthalmic solutions
 Ophthalmic solutions are sterile solutions, essentially
free from foreign particles, suitably compounded and
packaged for instillation into the eye .
e.g., Eye drops
Nasal solutions
 These solutions are sprayed or instilled into the nasal
cavity.
 E.g., Nose drops -administered by droppers and nasal
sprays
 Nasal solutions are most often used for local action,
but they may also be used for systemic effect.
 Solutions instilled into body cavities…

Otic solutions
 Otic solutions are sometimes referred to as ear
or aural solutions.
 They are usually placed in the ear canal by
drops in small amounts for removal of
excessive cerumen (earwax) or for treatment of
ear infections, inflammation, or pain.
 Eg., Cerumen-removing solutions like hydrogen
peroxide solution
 Solutions instilled into body cavities…
Enemas (rectal solutions)
 A number of solutions are administered rectally for local
effects (e.g., hydrocortisone) or for systemic absorption
(e.g.,aminophylline).
 Rectal enemas are also used to cleanse the bowel.
Vaginal douches (vaginal solutions)
 Vaginal douches are used for irrigation cleansing of the
vagina or treatment of infections
 Solutions for vaginal douches may be prepared from
powders or from liquid concentrates.
 Solutions instilled into body cavities…

Irrigation solutions
 These are sterile solutions used to soak, flush,
or irrigate wounds or body cavities, such as
the bladder.
 Since such solutions are administered to
vulnerable body tissues, they must be sterile
and should be handled in the same fashion as
parenteral products.
 Topical solutions
 Topical solutions are solutions applied topically,
that is to the skin, mainly for local action.
 They also include solutions applied to other
topical surfaces, such as the eye, ear and nose.
Glycerite
 Glycerite is solution of drug combined with at
least 50% glycerin for external use
Liniments
 Liniments are alcoholic or oleaginous solutions
or emulsions of various medicinal substances
intended to be rubbed on the skin.
 Topical solutions…
 Liniments with an alcoholic or hydroalcoholic
vehicle are useful when counterirritant, or
penetrating action is desired;
 Oleaginous liniments are employed primarily
when massage is desired.
 By their nature, oleaginous liniments are less
irritating to the skin than alcoholic liniments.
 Injectables (sterile products)
 Injectables are sterile, pyrogen limited, that is, bacterial
endotoxin units limit, preparations intended to be
administered parenterally.
 These are subdivided into:
 small volume parenteral fluids
 large volume parenteral fluids
 Small volume parenterals are sterile, pyrogen free
injectable products, packed in volumes up to 100 mL.

 Small volume parenterals are packed as:

 Single dose ampoules
 Multiple dose vials
 List examples for both!
 Injectables (sterile products)…
 Drugs destroyed or inactivated in the gastro-
intestinal tract or too poorly absorbed to
provide satisfactory response may be
prepared as injectables.
 Injectables are also preferred when rapid
absorption is essential, as in emergencies.
 In addition, they are useful in treating patients
who are uncooperative, unconscious, or
otherwise unable to accept oral medication.
General method of solutions preparation

 Most solutions are prepared by simply mixing of the

solutes with the solvent.

 For both small and large scale manufacture of

solutions equipment necessary are mixing vessels, a
means of agitation, & a filtration system to ensure
clarity of the final solution.

 During preparation, the solute is simply added to the

solvent in a mixing vessel & stirring is continued until
dissolution is complete.
 General method of preparation Cont…

 If the solute is more soluble at elevated temperature,

it may be advantageous to apply heat to the vessel
particularly if the dissolution rate is normally slow.

 Size reduction of solid materials to increase their

surface area also speed up the process of solution.
 Use of solubilizing agents
Methods to speed up dissolution of the
solute
– Applying heat
– Reducing the particle size of the solute
– Using a solubilizing agent
– Subjecting the ingredients to vigorous agitation