SOLUTIONS

Dr. Ayman Y. Waddad

Definition
 A homogenous one-phase system
consisting of two or more components
Solvent → phase in which the dispersion
occurs
Solute → component which is dispersed
as small molecules or ions in the solvent
Advantages (of Solutions as an
Oral Dosage Form):
1. Easier to swallow → suitable
for paediatrics and
geriatics.
2. Immediately available for
absorption → therefore there is
is faster therapeutic response.
3. Drug is uniformly distributed in
the formulation → promotes
dose uniformity.
4. There is reduced gastro-
intestinal irritation – since drug
is not localized in one area.
Disadvantages (of Solutions as an Oral Dosage
Form):
1. Liquids are bulky – inconvenient to transport and
store – there can be breakage → leading to
loss of product.
2. Stability of substance in aqueous solution is
often decreased → shelf-life is therefore shorter.
3. Promotes microbial growth → therefore require a
preservative.
4. Accurate dose to be administered
depends on patient.
5. Taste of drug → is more pronounced in
solution.
Aqueous
Solutions
 H O- is most widely used solvent in
2
pharmaceutical products → because of lack
of toxicity, physiological compatibility and the
ability to dissolve a wide range of materials.
Potable water can be used for oral
solutions. Alternatively → purified water BP.
For parenterals → water for injection BP.
Some drugs → require water for injection BP
free from CO2 and dissolved air.
 Approaches to
Improve Aqueous
1. Solubility
Cosolvency
2. pH Control
3. Solubilization
4. Complexation
5. Chemical modification
6. Particle size control
 1.
 Cosolvency
Solubility of a weak electrolyte or non-polar
compound in H2O can be improved by the addition
of a H2O miscible solvent in which the compound
is also soluble.
 Solubility of a given drug → maximal at a
particular dielectric constant → can be used as a
basis for selecting solvent blends.
 Suitable blends should posses a dielectric
constant of between 25-80.
 Water/ ethanol → most commonly used.
 Other suitable solvents → sorbitol,
glycerol.
 2. pH
 Control
If drug is a weak acid or weak base → solubility of
drug in H2O can be influenced by pH of the
system.
 Solubility of a weak base can be increased by
lowering the pH of its solution.
 Solubility of a weak acid can be increased by
raising the pH.
 Substance with two pKa values exhibit more
complex solubility profiles.
 Chosen pH must not interfere with other product
requirements e.g. chemical stability of drug,
stability of dyes, preservatives of flavours.
 pH of solutions for parenteral or ophthalmic use
must be controlled → because extremes can
cause pain and irritation.

 Compromise must be reached to ensure that

stability and solubility of excipients, physiological
compatibility and bioavailability are adequate for
intended purpose of product.
 3.
 Solubilization
Solubility of substance in H O can be improved by
2
the addition of a surfactant - phenomenon known
as → micellar solubilization.
 Quantity of surfactant must be optimized.
 Excess may be toxic and may affect bioavailability
of drug.
 Surfactants with HLB values > 15 are useful →
must be non-toxic and non irritant, miscible with
the solvent system, compatible with other
ingredients in the formulation, free from
disagreeable odour and taste, and non-volatile.
 4.

Complexation
Insoluble drug and soluble material may interact
and form a soluble intermolecular complex.
 Complex formation must be easily reversible so
that free drug is released during or before
contact with biological fluids e.g.
→ iodine with 10-15% PVP
→ salicylate with xanthines.
5. Chemical
Modification
 Involves chemical modification of a drug for
production of water soluble derivative.
 e.g.
→ sodium phosphate salts of hydrocortisone
→ chloramphenicol sodium succinate
 6. Particle Size
Control
 Size and shape of particles can affect solubility.
 ↓ particle size → leads to ↑ solubility.
 Little application to solutions → relevant to
suspensions.
 Non-aqueous
 Solutions
Alternative Solvents
May be used when drug is unstable in
aqueous solution/ incompletely dissolved →
use non- aqueous system.
Can be used for depot effect e.g. I.M injection
of testosterone.
Factors to consider → toxicity, irritancy,
sensitizing potential, flammability, stability,
compatibility with other excipients.
a) Fixed oils of vegetable origin
- Non-volatile oils which consist mainly of fatty acid
esters of glycerol e.g. Almond oil, arachis oil,
ethyl oleate, coconut oil

b) Alcohols
- Ethyl alcohol → widely used solvent.
- External application → evaporates rapidly and
has cooling effect.
- Isopropyl alcohol used externally.
c) Polyhydric alcohols
- Propylene glycol used in conjunction with H2O
or glycerol as a cosolvent
- Polyethylene glycols used in external preparations as
ointment bases
- Glycerol → widely used for oral preparations as
a cosolvent
d) Dimethyl sulphoxide
- Highly polar compound → used as
penetration enhancer
- Used as solvent in veterinary preparations
e) Ethyl ether
- May be used as a cosolvent with alcohol
for colloidions
- Not used on its own in pharmaceuticals
f) Liquid Paraffin
- Used as a solvent for topical application of drugs
- Not to be used in nasal preps

g) Other solvents
- Isopropyl myristate and palmitate used in cosmetics
→ non-greasy
- Xylene in ear drops
Formulation
Additives
1. Buffers
2. Colours
3. Flavours and perfumes
4. Preservatives
5. Antioxidants
6. Sweetening agents
 1. Buffers
 Materials when dissolved in solvent will enable
it to resist any changes in pH should acid/ alkali
be added.
 Depends on pH and buffering capacity
required.
 Must be compatible with other excipients and
have a low toxicity. Common pharmaceutical
buffer → carbonates, citrates, lactates,
phosphates, tartrates.
 Borates have been used in external preps.
 Injections, eye drops, nasal drops → buffered at
pH 7.4.
2.
Colours
 To improve attractiveness of prep
 Must complement flavour used
 Also used to mask degradation → if no effect
on therapeutic outcome.
 Natural and synthetic colours are available →
synthetics more widely used
 E.g. amaranth (FD & C red no. 2)
 3. Flavours &

Perfumes
The use of sweetening agents only may not
be sufficient to render a product palatable.
 Useful in paediatric formulations → to improve
patient compliance.
 May be natural or synthetic.
 Natural → fruit juices, aromatic oils,
peppermint and lemon oils.
 Synthetic → cheaper and more readily
available.
4. Preservatives
 Adsorption of preservative from product onto
container must not occur.
 pH of solution must not affect preservative
efficacy.
 Must not interact with excipients e.g. parabens
can be adsorbed onto micelles of non-ionic
surfactants.
 Microbial challenge test to assess efficacy of
preservative system ( refer to suspensions and
emulsions) should be done.
5.
Antioxidants
 Decomposition of solutions in which drug
undergoes oxidation can be controlled by the
addition of antioxidants.
 6. Sweetening
 Agents
Low molecular weight carbohydrates widely used.
 In particular sucrose is most widely used.
 Advantage – colourless, very soluble in H2O,
stable over pH range 4-8, masks taste of salty and
bitter drugs.
 Polyhydric alcohols → sorbitol, mannitol, glycerol
used as sweeteners → included in diabetic
preparations.
 Hydrogenated glucose syrup, isomalt, fructose
and xylitol are also used.
 Artificial sweetners → can be used in
combination with sugars and alcohols or on their
own.
 Require small quantities because hundreds or
thousands times sweeter than sucrose.
 Used in concentrations not greater than 0.2%
e.g. sodium or calcium saccharin.
 Highly water soluble and chemically and
physically stable over wide pH range.
 Disadvantage - impart bitter or metallic after
taste.
1) Mixtures and draughts
- Mixture → aqueous preparation mostly
manufactured on a small scale with a shelf-life of a
few weeks.
- Draughts → mixtures of which only one or two
large doses of ± 50mL are given.

2) Elixirs
- Clear, sweetened
hydroalcohol liquids for oral use:
Contains flavouring substances/
Drug
3)
Linctuses
- A viscous preparation usually prescribed for the
relief of cough.
- Usually contains simple solution of active in a
high concentration of sucrose.
- Should be sipped slowly and should not be
diluted prior to administration.
4) Mouth washes & gargles
- Aqueous solutions for the prevention and treatment
of mouth and throat infections.
- Contains antiseptics, analgesics and/or astringents.
5) Nasal products
- Small volume solutions in an aqueous vehicle
- pH should be 6.8
- Has to be isotonic
- Should be made viscous

6) Ears drops
- Simple solutions of drugs in water, glycerol, propylene
glycol or alcohol/water mixtures
7)
Enemas
- Aqueous or oily solutions for rectal
administration
- For cleansing, diagnostic or therapeutic effect.

8) Preparations for External Use

- Lotions - formulated as solutions -
applied to skin without friction.
- Liniments - intended to be massaged
into skin.
- Paints - to obtain film of drug on skin.
Manufacturing of
Solutions
 For both small and large scale-only
equipment required is suitable mixing
vessels, a means of agitation and a
filtration system to ensure clarity.
 Size of materials can be reduced-solute
simply added to solvent in a mixing
vessel.
Stirred until complete dissolution. May use
heat.
 Volatile substances e.g. perfume added
after cooling.
 Filtered to ensure clarification.
 Stability of

Solutions
Chemical and physical stability in intended
containers is important.
 Must retain clarity, colour, odour, taste, viscosity
for duration of shelf-life.
 Clarity and colour assessed by visual examination
or spectrophotometrically.
 Viscosity assessed by rheological assessment.
 Stability of flavours and perfumes more difficult to
assess → chromatography/ panel of assessors.
 Active Drug → assessed by HPLC etc.