Solution

A solution is a homogeneous mixture prepared by dissolving a solid, liquid or gas in

another liquid and represents a group of preparation in which the molecules of solute
or dissolved substances are dispersed among those of the solvent. Solution dosage form
includes-
1. Solution for internal use
a. Syrups
b. Elixirs
c. Aromatic water etc.
2. Solution for external use
a. Lotions
b. Liniments

Syrups:
Syrups are viscous, sweet, concentrated solutions of sugar such as sucrose in water
or other aqueous liquid. In addition to sucrose, syrups may contain glycerin,
sorbitol, propylene glycol etc.
Syrups are used for formulating antibiotics, antitussives, antihistamines, sedative,
vitamins etc.
Elixirs:
Elixirs are clear, pleasantly flavored oral liquids containing one or more active
ingredients dissolved in a vehicle that usually contains a high proportion of sucrose
or a suitable polyhydric alcohols or alcohols. The alcohol content in most elixirs
usually varies from 4 to 40 %. e.g. Phenobarbitone elixirs (anticonvulsant).

Aromatic Water:
Aromatic waters are clear saturated aqueous solution of volatile oils or other
aromatic substances, usually employed for their flavoring rather than medicinal
properties although a few of them have therapeutic activity. e.g. Rose water,
Chloroform water.

Lotions:
Lotions are liquid or semi-liquid preparations which are
applied to unbroken skin without friction. They are
either dabbed on the skin or applied on a suitable
dressing and covered with waterproof material to reduce
evaporation. Lotions generally contain antiseptics,
astringents, anesthetics, protective agents for prevention Figure: Aromatic Water
or treatment of various skin diseases.
e.g. Salicylic acid lotion, hydrocortisone lotion.
Liniments:
Liniments are liquid or semi-liquid preparations, which are applied to unbroken skin
by friction or applied on lint or other suitable material and placed on the affected
part.
The oily or soapy liniments are milder in their action but are more useful when
massage is required.
e.g. Camphor liniments (counter irritant)

Figure: Lotion application

Figure: Liniment application to skin

Advantages Solution:
 Rapid absorption: The drug is more readily available for absorption from
liquid dosage forms as compared to solids.
 Ease of swallow: Liquids are easier to swallow than tablets or capsules and are
therefore especially suitable for children and the elderly.
 Reduction of gastric irritation: Gastric irritation due to certain drugs like
aspirin and potassium chloride when administered as a solid dosage form is
avoided or reduced on administration as a solution.
 Dose adjustment: The doses of drugs can be easily adjusted according to the
need of the patient.
 Cost: Liquid dosage forms are more economical to produce than solid dosage
forms.
 Distribution of drugs: Distribution of drug in liquid dosage forms is better than
solid dosage forms.
 Large dose: Drugs with large dose can be easily administered as liquid dosage
form.

Disadvantages:
 Stability problem: Drugs are usually less stable in liquid dosage forms as
compared to solid dosage forms like tablets and capsules.
  Dose variation: Administration of correct dose is less precise since it depends
on the ability of the patient to measure the correct dose using a suitable
measuring device such as a spoon or a dropper.
 Enhance the growth of microorganism: Liquids especially aqueous preparation
are susceptible to microbial contamination.
 Difficult to mask unpleasant taste: Masking the unpleasant taste of a drug in
solution is more difficult than when the drugs in a solid dosage form.
 Inconvenient to store and carry: Liquid preparations are usually bulky and
therefore inconvenient to store and carry.

Composition
Solvent + Solute
Solvent is that phase in which the dispersion occurs.
Solute is that component which is dispersed as small molecules or ions in the
solvent.
The solution of glucose in water where glucose is solute and water is a solvent.

Methods of expressing composition or concentration: A number of methods are

employed to express the relative amounts of the components of a solution in
quantitative terms.
Percentage:
Expression Abbreviated Meaning and Example
expression

Percent weight % w/v Grams of constituent in 100 ml of preparation. e.g.

in volume 1% w/v = I g constituent in 100 ml preparation.

Percent volume % v/w Milliliters of constituent in 100 g of preparation. e.g.

in weight 1% v/w = I ml constituent in 100 g preparation.

Percent weight % w/w Grams of constituent in 100 g of preparation. e.g. 1%

in weight w/w = I g constituent in 100 g preparation.

Normality:
Normality is the equivalent weight of a solute dissolved in one liter of the solution.
Normality= equivalent wt. of a solute/1 liter of solution.

Molarity:
Molarity is the number of moles of solute dissolved in one liter of a solution.
Molarity= Numbers of moles of solute/1 liter of solution

Molality:
Molality is the number of molecules of a solute in 1000 gm of solvent.

Mole fraction:
Mole fraction is the ratio of the moles of solute to the total moles of the solution (i.e.
moles of solute and solvent).

Mole fraction of solute (x1) =n1/(n1+n2)

Where, n1=number of moles of solute
n2= number of moles of solvent

Classification:
Solution are classified in various ways
1. Depending upon the states of solute and solvent
a. Gas in gas e.g. Atmospheric air
b. Liquid in gas e.g. Aerosol, fog
c. Solid in gas e.g. Dust
d. Gas in liquid e.g. Soda water ( carbonated water)
e. Liquid in liquid e.g. Solution of water and ethanol
 f. Solid in liquid e.g. Saline water
g. Gas in solid e.g. H2 in platinum, cork
h. Liquid in solid e.g. Oil in paraffin
i. Solid in solid e.g. alloy

2. Depending on saturation
a. Saturated solution
b. Unsaturated solution
c. Supersaturated solution

Saturated solution: Solution containing maximum amount of solute at a particular

temperature and pressure and the homogeneity is destroyed by further addition of
solute is called saturated solution.

Unsaturated solution: The solution that contain less amount of solute than in the
saturated solution at the same temperature and pressure and further addition of
solute is possible is called unsaturated solution.
 Supersaturated solution: The solution that contain more amount of solute than
saturated solution due to special reasons at a particular temperature and pressure
is called supersaturated solution.

Depending on the method of preparation:

a. Simple solution
b. Compound solution

Simple solution: The solution which is formed by dissolving of only one active
ingredient in the solvent is called simple solution.

Compound solution: When more than one ingredient are dissolved in the solvent,
the preparation is called compound solution.

Depending on the solvent used:

a. Aqueous solution
b. Non-aqueous

Aqueous solution: The solution in where water is used as a solvent are referred to
as aqueous solution
 Nonaquous solution: The solution having vehicle other than water is called non-
aqueous solution.

Formulation of solution
The following factors must be considered during the formulation of an acidic or
basic drugs.

1. The solubility of ionized and non-ionized forms of the drugs

2. The chemical stability of the drugs.
3. The therapeutic efficacy of the drug

Additives:
Additives are substances (other than the active ingredients) which
are included during the formulation of a dosage form but do not have any
therapeutic activity of their own.

Additives mainly serve as an aid to drug formulation. A number of additives are

employed during the formulation of a solution. These include-
• Vehicles
• Viscosity enhancing agents
 • Preservatives
• Antioxidants
• Sweetening agents
• Flavoring agents
• Coloring agents etc.
• Buffer
• Isotonocity Modifiers

Vehicles:
Vehicles are substances which serve as medium in which other ingredients of a
formulation are dissolved or dispersed. The most commonly used vehicles in liquid
formulation include
• Water
• Aromatic water
• Syrups
• Glycerol
• Polyethylene glycol
 • Propylene glycol
• Ethanol
• Isopropyl alcohol
• Oils (mineral and vegetative oils)

Water:
Water is the most common vehicle used in pharmaceutical preparations. This is
for the following reasons
– Nontoxic
– It does not interfere with the normal metabolic activity of the body.
– A wide range of materials dissolve in water
– Available
– Tasteless, colorless and odorless.
– Nonirritant
– It has no pharmacological effect
– Its purity is constant
– Easy to store
Different types of water are available.
a. Potable water:
Potable water is water mainly derived from surface sources such as lakes, rivers
and streams or underground sources such as spring or well. Its chemical
composition depends upon the source from which it is drawn.
The mineral impurities that it contains should not react with the medicaments or
other ingredients.

b. Purified water:
Purified water is water prepared from suitable potable water by distillation, ion-
exchange treatment, reverse osmosis or by any other suitable method.

c. Water for injection (WFI):

Water for injection is pyrogen-free distilled water intended for use in the
preparation of parenteral administration.
It is usually prepared by distilling potable water, purified water or distilled water.

d. Sterile water for injection:

Sterile water for injection is a special type of WFI that has been sterilized and
packed in suitable containers to ensure that it remains totally apyrogenic.

Glycerol:
• Glycerol is a viscous polyhydric alcohol.
• It is mainly used as a vehicle for some external preparations such as ear drops
• It also act as a co-solvent with water in solutions for internal use.
• It also act as a sweetening agent and in concentration above 20% it acts as a
preservatives.

Propylene glycol:
• Propylene glycol is also used as a solvent for external preparations and as a co-
solvent with water for internal preparations.
• At a concentration above 30%, it inhibits mould growth and fermentation.
Polyethylene glycol:
• Low molecular weight polyethylene glycols such as PEG 200, 300, 400 etc.
are liquid at room temperature.
• They also employed as solvents and co solvents in different liquid preparation.
• They are miscible with water.

Ethanol:
• Ethanol is very useful solvent for both internal and external solutions.
• It is miscible with water in all proportions.
 • It is also miscible with other solvents or vehicles of liquid preparations.
• Alcohol has antimicrobial properties.
• It also prevents hydrolysis of certain drugs.

Isopropyl alcohol:
• Isopropyl alcohol has solvent properties similar to ethanol.
• It has a typical odour which is difficult to mask.

Viscosity-enhancing agents:
Viscosity-enhancing agents, also known as viscosity modifiers or thickeners, are
commonly used in pharmaceutical solutions to increase their thickness and
improve their properties, such as stability, bioavailability, or ease of handling.

Examples include natural polymers like carrageenan and gellan gum, cellulose
derivatives such as methylcellulose and hydroxypropyl methylcellulose (HPMC),
and synthetic polymers like polyvinyl alcohol.

Preservatives:
Substances added to pharmaceutical preparations to protect them from chemical
change or microbial action. They include anti-bacterial agents and antioxidants.
Common preservatives include parabens, benzoic acid, sodium benzoate, and
phenoxyethanol.

Antioxidants:
Antioxidants are substance that are added to pharmaceutical preparations to
prevent oxidative degradation of liable substances in the preparation.
An ideal antioxidant should have the following criteria
• Nontoxic
• Nonirritant
• They should be effective at low concentration under the expected conditions of
storage and use
• They should be soluble in the vehicle
• They should be stable.
• Antioxidant for use in oral preparations should also be odorless and tasteless.

Commonly used antioxidants for liquid include-

• Ascorbic acid
• Sodium sulphite
• Sodium metabisulphite
 • Tocopherol
• Propyl gallate
• Butylated hydroxytoluene and (BHT)
• Butylated hydroxylanisole (BHA)

Sweetening agents
Sweetening agents are substances added to formulation to mask the objectionable
taste of the active ingredient and make the preparation more palatable.
Commonly used sweetening agents for liquid include
• Glucose
• Sucrose
• Honey
• Sorbitol
• Mannitol
• Xylitol
Artificial sweeteners include-
• Sodium and calcium salts of saccharine- they are very soluble in water to form
stable solutions over a wide pH ranges.
• Aspartame- it has been increasingly used as a sweetening agent in recent years
especially for sweetening foods and drinks. But it hydrolyses in solution
especially when heated at high temperature.

Flavouring agents:
Flavouring agents are used to mask unpleasant taste and odor of active substances
and to make medicines more acceptable to patients, especially children.

Necessity:
• To render palatability of a product containing a drug with a unpleasant taste
• To ensure patient compliance in case of pediatric formulations.
• To overcome unpleasant odor.
• To identify the liquid products.
• To satisfy marked demand.
• To encourage continuation of the treatment.
Example:
• Sweet fruit-flavour- children usually prefer this type of flavor.
• Chocolate
• Anise
• Menthol
• Cinnamon
• Butterscotch

Coloring agents:
Coloring agents are generally added to liquid preparations to mask an unpleasant
appearance or to increase the acceptability of the preparation to the patients.
Acceptability may be enhanced by inclusion of a color that is closely associated
with the flavor of the preparation.
Colorants to be used should be nontoxic, nonirritant and compatible with active
ingredients and other ingredients of the preparation.

Necessities:
• To increase drug acceptability by improving the attractiveness of the product.
• To give warning.
• To produce standard preparation by giving uniform appearance to the
pharmaceutical preparations.
• To mask an innocuous colour change.

There are three categories of coloring agents-

 Mineral pigments- iron oxides
• Natural colorants and – anthocyanins, carotenoids, chlorophyll, xanthophylls,
riboflavine, saffron, cochineal and caramel.
• Synthetic organic dyes.- Erythrosine, carmoisine, brilliant blue, sunset yellow
quinoline yellow, tartrazine etc.

Buffers:
Buffers are the mixture of weak acids and its salt or weak base and its salt.
When this mixture is dissolved in a solvent, it will enable to resist any change of pH
upon the addition of small quantities of acid or alkali.

Necessity:
• To increase the stability
• To increase the solubility of the drug.
• To minimize pain, irritation and necrosis on injection.
• To provide unsuitable preparation for micro-organism.
• To enhance the biological activity of the drug.

Pharmaceutical used buffer

• Boric acid buffer :pH 8-
10
• Acetic acid buffer :pH 4-6
• Benzoic acid buffer :pH 3-5
Phosphoric acid buffer :pH 1-3
•

Isotonocity Modifiers:
When two solutions are separated by a semi permeable membrane, if there is no
diffusion of solvents through the membrane i.e. their osmotic pressure are same
then the solutions are called isotonic.
Eg. 0.9% NaCl is isotonic to blood.
Solubility:
According to the U.S. Pharmacopeia and National Formulary, the solubility of
drugs may be defined as the number of milliliters of solvent in which 1 gm of solute
will dissolve at a particular temperature.

For example, the solubility of boric acid in water and alcohol is 18 because 1 gm of
boric dissolves in 18 ml water/alcohol. It is 4 in glycerine because 1 gm of boric
acid dissolves in 4 ml glycerine.
Ways to improve solubility of a compound:

Solubilization:
Solubilization may be described as the dissolution of poorly soluble solute
molecules in water in the presence of surfactants.
When surfactants with proper HLB values are dispersed in water up to a certain
concentration their molecules tend to concentrate at the interface between the water
and the air until all available space is saturated.
Beyond that concentration, technically referred to as the critical micelle
concentration (C.M.C.) the surfactant molecules descend into the main body of the
solvent phase where they tend to aggregate in to groups of 100150 molecules
known as micelles.
The mechanism for the solubilization involves the property of surface active agents
to form colloidal aggregates known as micelle.

When surfactants are added to a liquid at low concentrations, they tend to orient at
the air-liquid interface. As additional surfactant is added, the interface becomes
fully occupied and the excess molecules are forced into the bulk of the liquid.

At still higher concentrations, the molecules of surfactant in the bulk of the liquid
begin to form oriented aggregates or micelles. The concentration of surfactants at
which it occurs is known as critical micelle concentration.
The solute molecules are dissolve or absorbed on to the micelle. Thus, ability of
surfactants solutions to dissolve or solubilize water insoluble materials starts at the
CMC and increases with the concentration of micelle.
Complexation:
Complexation is the process of increasing solubility of a poor soluble drug by the
interaction with a soluble material to form a soluble intermolecular complex.
It is however essential that the complex formed is easily reversible so that the free
drug is released readily during or before contact with biological fluid.
For example, Iodine is relatively insoluble in water but povidone is soluble. The
interaction/complexation of Iodine with povidone to form water soluble Povidone-
Iodine complex.
Fig: Povidone-Iodine

Hydrotropism:
Hydrotropism is the term used to describe the increase in aqueous solubility of a
drug by the use of large concentrations (20% to 50%) of certain additives.
For example,
1. The solubility of caffeine is very appreciably improved by the addition of
sodium benzoate.
2. The solubility of theophylline is improved by the addition of sodium
salicylate.

Chemical Modification of Drug:

Many substances, poorly soluble in water can be modified in to derivatives with
appreciable solubility in water. For instances hydrocortisone, prednisolone and
betamethasone are modified to their sodium phosphate salts.
Betamethasone alcohol –solubility 5.8 mg / 100 ml.
When it is converted to disodium phosphate ester gives a solubility of 10gm/ 100
ml (i.e. 1500 fold increase).
 Particle size control:
The size and shape of very small particles can affect solubility. As particle size
decreases solubility will increase.

Effect of molecular structure on solubility:

On the basis of structural similarity between solvents and solutes, solvent dissolve
some solute quite readily and others slightly or not at all.
• The more similarity between structure of solvents and solute, the more readily
solution take place.
• Polar liquid dissolved electrovalent compounds readily but they are poor
solvents for nonpolar solutes and vice versa.
• Polar liquid will be miscible with polar liquids. Nonpolar liquids dissolves
slightly on polar liquid but completely in nonpolar solvents.

Formulation of Solution:
 Active ingredient
 Solvent
 Preservative
 Antioxidant
 Buffer
 Coloring agent
  Flavoring agent
 Sweetening agent

Manufacturing steps of solution preparation:

 Solution are manufactured by the direct mixing of the drugs with solvent.
There is no hard and fast rule for mixing.
• The solute is simply added to the solvent in a mixing vessel and stirring is
continued until dissolution is completed.
• If the solute is more soluble at elevated temperatures, it may be advantageous
to apply heat to the vessel particularly if dissolution rate is slow.
• Size reduction of solid materials help to increase the total surface area as well
as the speed up the process of solution.
• Other additives are also added depending on the solution types.
• Solute present in low concentration especially dyes are often pre-dissolved in
small volume of the solvent and then added to the bulk.
• Volatile materials such as flavors or perfumes are added at the end of process
and often after cooling if necessary to reduce loss of evaporation.
• To ensure clarity of final solution filtration is done.
• After ensuring the clarity the final product is stored in suitable container.